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Find video protocols related to scientific articles indexed in Pubmed.
Delayed wound healing after forefoot surgery in patients with rheumatoid arthritis.
Mod Rheumatol
PUBLISHED: 11-11-2014
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Objective. To elucidate the systemic and local risk factors and the effect of surgical procedures for delayed wound healing after forefoot surgery in patients with rheumatoid arthritis (RA). Methods. Fifty forefoot surgeries were performed in 39 patients using resection arthroplasty or a joint-preserving procedure (25 feet for each procedure). The associations between the occurrence of delayed wound healing and clinical variables, radiological assessment, or surgical procedures were analyzed. Results. Delayed wound healing was recorded in nine feet of eight patients. The duration of RA was significantly longer in the delayed healing group than that in the healed group. Age, sex, smoking history, concomitant diabetes, and RA medication did not differ between the groups. Radiological evaluation showed significant differences between groups in metatarsophalangeal dorsal flexion angle. The shortened length of the fourth and the fifth metatarsal bones affected the occurrence of the complication. The joint-preserving procedure had significantly less delayed wound healing compared with resection arthroplasty. Conclusions. Preoperative dorsoplantar deformity and perioperative tissue damage can cause delayed wound healing after forefoot surgery in RA patients.
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Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease.
Science
PUBLISHED: 10-18-2014
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T cells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity.
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Malrotated tibial component increases medial collateral ligament tension in total knee arthroplasty.
J. Orthop. Res.
PUBLISHED: 08-29-2014
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Malrotation of the tibial component can lead to complications after total knee arthroplasty (TKA). Despite reports of internal rotation being associated with more severe pain or stiffness than external rotation, the biomechanical reasons remain largely unknown. We used a computer simulation model and evaluated traction forces in the lateral collateral ligament (LCL) and medial collateral ligament (MCL) with a malrotated tibial component during squatting. We also examined tibiofemoral and patellofemoral contact forces and stresses under similar conditions. A dynamic musculoskeletal knee model was simulated in three different constrained tibial geometries with a prototype component. The testing conditions were changed between 15° external and 15° internal rotation of the tibial component. With internal rotation of the tibial component, the MCL force increased progressively; the LCL force also increased, but only up to less than half of the MCL force values. A higher degree of constraint of the tibial component was associated with greater femoral rotational movement and higher MCL forces. The tibiofemoral and patellofemoral contact forces were not influenced by malrotation of the tibial component, but the contact stresses increased because of decreased contact area. This altered loading condition could cause patient complaints and polyethylene problems after TKA. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1658-1666, 2014.
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MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.
PLoS ONE
PUBLISHED: 08-18-2014
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The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models.
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Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect.
J Clin Biochem Nutr
PUBLISHED: 06-20-2014
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Photodynamic therapy using hematoporphyrin and its derivatives is clinically useful for cancer treatments. It has been reported that cancer cells incorporate hematoporphyrin and its derivatives via heme carrier protein 1, which is a proton-coupled folate transporter. However, the mechanism of this protein expression has not been elucidated. In general, the concentration of reactive oxygen species in cancer cells is higher than that in normal cells. We previously reported that reactive oxygen species from mitochondria involved in the expression of peptide transporter 1 and accelerate the uptake of 5-aminolevulinic acid, which is a precursor of protoporphyrin IX. We suggested mitochondrial reactive oxygen species also regulated the expression of heme carrier protein 1. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1. We clarified the expression of heme carrier protein 1 increased in cancer cells and it decreased in manganese superoxide dismutase expressed cancer cells. In addition, the uptake level of hematoporphyrin and photodynamic therapeutic effect were also decreased in manganese superoxide dismutase expressed cancer cells in comparison with cancer cells. Thus, we concluded that mitochondrial reactive oxygen species regulated heme carrier protein 1 expression and photodynamic therapeutic effect.
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Acetaldehyde is an oxidative stressor for gastric epithelial cells.
J Clin Biochem Nutr
PUBLISHED: 05-30-2014
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Alcohol drinking and smoking contain the risk of a carcinogenesis. Acetaldehyde is content in cigarette smoke and an ethanol metabolite. However the clear evidence for reactive oxygen species (ROS) generation by acetaldehyde in gastric cells in vitro is none. In this study, we elucidated acetaldehyde is an oxidative stress inducer on rat gastric epithelial cells by electron paramagnetic resonance measurement in living cells. We also confirmed whether acetaldehyde-induced cellular ROS was derived from mitochondria or not. The results of cellular ROS determination showed that an increment of cellular ROS was shown for 15 min in living cells from exposing 0.1% (v/v) acetaldehyde. Lipid peroxidation in cellular membrane also induced by 0.1% ethanol and the tendency is same in the results of cellular ROS determination. JC-1 stained showed the decrement of mitochondrial membrane potential. These results indicated that acetaldehyde is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer via injured mitochondria.
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The KSS 2011 Reflects Symptoms, Physical Activities, and Radiographic Grades in a Japanese Population.
Clin. Orthop. Relat. Res.
PUBLISHED: 04-30-2014
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Cultural and ethnic differences are present both in subjective and objective measures of patient health, but scoring systems do not always reflect these differences, and so validation of outcomes tools in different cultural settings is important. Recently, a revised version of The Knee Society Score(®) (KSS 2011) was developed, but to our knowledge, the degree that this tool evaluates clinical symptoms, physical activities, and radiographic grades in the general Japanese population is not known.
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TNF?, PDGF, and TGF? synergistically induce synovial lining hyperplasia via inducible PI3K?
Mod Rheumatol
PUBLISHED: 04-11-2014
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Objectives. To determine the mechanism underlying hypertrophic synovium in rheumatoid arthritis (RA). Methods. We examined micromass cultures of fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor ? (TNF?), platelet-derived growth factor (PDGF), and/or transforming growth factor ? (TGF?). The hypertrophic architecture of the micromasses, expression of phosphoinositide 3 kinase (PI3K) isoforms, and persistent activation of PI3K-Akt pathways were investigated. FLSs transfected with siRNA were also examined in the micromass cultures. Results. The combination of TNF?, PDGF, and TGF? (TPT condition) induced obvious hypertrophic architecture of the intimal lining layer in FLSs in micromass cultures, and was accompanied by upregulated expression of matrix metalloproteinase-3 (MMP3), Cadherin-11, and PI3K?. In monolayer FLSs, the TPT condition enhanced the expression of PI3K? and persistent activation of the PI3K-Akt pathway. Knockdown of PI3K? significantly inhibited the formation of the hypertrophic synovial lining in the TPT condition. Conclusions. These results collectively indicate that inducible PI3K? plays a crucial role in persistent activation of PI3K-Akt in FLSs, and in the formation of a hypertrophic synovial lining. PI3K? may be an alternative treatment target for the regulation of proliferative synovium in RA.
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Clinical considerations of regenerative medicine in osteoporosis.
Curr Osteoporos Rep
PUBLISHED: 03-13-2014
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Osteoporosis-related fractures may severely limit activities of daily living and may require bed rest, which may become life threatening in elderly people. Osteoporosis has attracted much attention recently because of its severe effects on the daily activities of older people and because it is now treatable, thanks to recent advances in drug discovery. However, these medications have yet to reduce fully the number of fracture cases. On the other hand, declines in the number and function of osteoblasts and mesenchymal stem cells (MSCs) in the bone marrow and within the periosteum lead to reduced osteogenesis and bone formation. Thus, bone regeneration, through induction of MSCs, provides a rational therapeutic strategy for preventing or treating age-related osteoporosis. In this review, I summarize cell-related issues in osteoporosis, stem cell candidates for cell-based therapy, and possible therapeutic strategies for osteoporosis.
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LOTUS suppresses axon growth inhibition by blocking interaction between Nogo receptor-1 and all four types of its ligand.
Mol. Cell. Neurosci.
PUBLISHED: 03-11-2014
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Axon growth inhibitors such as Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and B lymphocyte stimulator (BLyS) commonly bind to Nogo receptor-1 (NgR1), leading to enormous restriction of functional recovery after damage to the adult central nervous system. Recently, we found that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated Nogo signaling. However, whether LOTUS exerts antagonism of NgR1 when bound by the other three ligands has not been determined. Overexpression of LOTUS together with NgR1 in COS7 cells blocked the binding of MAG, OMgp, and BLyS to NgR1. In cultured dorsal root ganglion neurons in which endogenous LOTUS is only weakly expressed, overexpression of LOTUS suppressed growth cone collapse and neurite outgrowth inhibition induced by these three NgR1 ligands. LOTUS suppressed NgR1 ligand-induced growth cone collapse in cultured olfactory bulb neurons, which endogenously express LOTUS. Growth cone collapse was induced by NgR1 ligands in lotus-deficient mice. These data suggest that LOTUS functions as a potent endogenous antagonist for NgR1 when bound by all four known NgR1 ligands, raising the possibility that LOTUS may protect neurons from NgR1-mediated axonal growth inhibition and thereby may be useful for promoting neuronal regeneration as a potent inhibitor of NgR1.
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Is a "sulcus cut" technique effective for determining the level of distal femoral resection in total knee arthroplasty?
Knee Surg Sports Traumatol Arthrosc
PUBLISHED: 03-01-2014
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Determining the level of distal femoral resection is crucial when performing total knee arthroplasty (TKA). However, variations in distal femoral resection are encountered unexpectedly. A "sulcus cut" technique is sometimes used to determine the level of distal femoral resection, but its effectiveness has not been evaluated. The aim of this study was to examine the reliability of the sulcus cut technique using computer simulation for preoperative planning.
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Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells.
J Clin Biochem Nutr
PUBLISHED: 03-01-2014
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Photodynamic therapy and photodynamic diagnosis using 5-aminolevulinic acid (ALA) are clinically useful for cancer treatments. Cancer cells have been reported that 5-aminolevulinic acid is incorporated via peptide transporter 1, which is one of the membrane transport proteins, and has been reported to be significantly expressed in various gastrointestinal cancer cells such as Caco-2. However, the mechanism of this protein expression has not been elucidated. Concentration of reactive oxygen species (ROS) is higher in cancer cells in comparison with that of normal cells. We have previously reported that ROS derived from mitochondria is likely related to invasions and proliferations of cancer cells. Since 5-aminolevulinic acid is the most important precursor of heme which is necessary protein for cellular proliferations, mitochondrial ROS (mitROS) may be also related to peptide transporter 1 expressions. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1, and we clarified the ALA uptake mechanism and its relations between mitROS and peptide transporter 1 expression in RGK1. We also used our self-established stable clone of cell which over-expresses manganese superoxide dismutase, a mitROS scavenger. We studied differences of the photodynamic therapy effects in these cells after ALA administrations to clear the influence of mitROS.
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MicroRNA-451 down-regulates neutrophil chemotaxis via p38 MAPK.
PUBLISHED: 02-28-2014
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MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate the activity of target messenger RNAs (mRNAs) and cellular processes. MicroRNA-451 (miR-451) is one of the miRNAs that is conserved perfectly among vertebrates, and it regulates cell proliferation, invasion, and apoptosis in tumors. However, the role of miR-451 in autoimmune arthritis is unknown. This study was undertaken to identify the role of miR-451 in autoimmune arthritis.
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Evolutionary optimality in sex differences of longevity and athletic performances.
Sci Rep
PUBLISHED: 02-27-2014
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Many sexual differences are known in human and animals. It is well known that females are superior in longevity, while males in athletic performances. Even though some sexual differences are attributed to the evolutionary tradeoff between survival and reproduction, the aforementioned sex differences are difficult to explain by this tradeoff. Here we show that the evolutionary tradeoff occurs among three components: (1) viability, (2) competitive ability and (3) reproductive effort. The sexual differences in longevity and athletic performances are attributed to the tradeoff between viability (survival) and competitive ability that belongs to the physical makeup of an individual, but not related to the tradeoff between survival and reproduction. This provides a new perspective on sex differences in human and animals: females are superior in longevity and disease recovery, while males are superior in athletic performance.
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In vivo femoro-tibial kinematic analysis of a tri-condylar total knee prosthesis.
Clin Biomech (Bristol, Avon)
PUBLISHED: 02-17-2014
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An alternative tri-condylar implant has been designed to incorporate necessary posterior stability without a post, but has not been evaluated. The purpose of the current study was to determine the in vivo three dimensional femoro-tibial kinematics of a tri-condylar implant during a weight bearing deep knee bend activity.
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Tibial Rotational Alignment Was Significantly Improved by Use of a CT-Navigated Control Device in Total Knee Arthroplasty.
J Arthroplasty
PUBLISHED: 01-15-2014
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This study compared the accuracy of three methods to set tibial component rotational alignment: (1) conventional method, the anteroposterior (AP) axis was determined by the surgeon using anatomical landmarks; (2) partial-navigation method, the tibia was prepared according to the AP axis using a CT-based navigation system and the component was manually positioned; (3) full-navigation method, the tibial component was positioned and fixed with cement under the control of navigation using a newly developed instrument. The conventional method showed considerable deviation (range, -18.6° to 14.7°), and the partial-navigation method also showed considerable deviation (-11.3° to 8.1°). In contrast, the full-navigation method significantly improved the accuracy of alignment (-2.9° to 2.1°). The tibial component can become malaligned during cement fixation, even after proper bone preparation.
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Self-assessment tool of disease activity of rheumatoid arthritis by using a smartphone application.
Telemed J E Health
PUBLISHED: 01-03-2014
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The disease activities of rheumatoid arthritis (RA) tend to fluctuate between visits to doctors, and a self-assessment tool can help patients accommodate to their current status at home. The aim of the present study was to develop a novel modality to assess the disease activity of RA by a smartphone without the need to visit a doctor.
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Increase of hemoglobin levels by anti-IL-6 receptor antibody (tocilizumab) in rheumatoid arthritis.
PLoS ONE
PUBLISHED: 01-01-2014
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To compare the effect of tocilizumab (TCZ) with other biologic therapies in improving anemia of rheumatoid arthritis (RA) patients.
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Inverse association between air pressure and rheumatoid arthritis synovitis.
PLoS ONE
PUBLISHED: 01-01-2014
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Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p = 1.7 × 10(-7), 0.00027, and 8.3 × 10(-8), for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA.
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Are the long term results of a high-flex total knee replacement affected by the range of flexion?
Int Orthop
PUBLISHED: 10-17-2013
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The purpose of this study was to examine the effect of deep flexion on the long-term durability of a high-flex ceramic implant in total knee arthroplasty.
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Development of lifelog sharing system for rheumatoid arthritis patients using smartphone.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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In this paper, we report the development of a lifelog sharing system for rheumatoid arthritis patients. Our system can objectively assess patients condition from day to day via their smartphone use. We conducted a field experiment to investigate the feasibility of lifelog collection and sharing. The rate of patient assessment is very high. The system collects daily change in patients activity as influenced by the disease.
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The O-C2 angle established at occipito-cervical fusion dictates the patients destiny in terms of postoperative dyspnea and/or dysphagia.
Eur Spine J
PUBLISHED: 08-06-2013
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We have revealed that the cause of postoperative dyspnea and/or dysphagia after occipito-cervical (O-C) fusion is mechanical stenosis of the oropharyngeal space and the O-C2 alignment, rather than total or subaxial alignment, is the key to the development of dyspnea and/or dysphagia. The purpose of this study was to confirm the impact of occipito-C2 angle (O-C2A) on the oropharyngeal space and to investigate the chronological impact of a fixed O-C2A on the oropharyngeal space and dyspnea and/or dysphagia after O-C fusion.
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The paradox of enrichment in phytoplankton by induced competitive interactions.
Sci Rep
PUBLISHED: 06-13-2013
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The biodiversity loss of phytoplankton with eutrophication has been reported in many aquatic ecosystems, e.g., water pollution and red tides. This phenomenon seems similar, but different from the paradox of enrichment via trophic interactions, e.g., predator-prey systems. We here propose the paradox of enrichment by induced competitive interactions using multiple contact process (a lattice Lotka-Volterra competition model). Simulation results demonstrate how eutrophication invokes more competitions in a competitive ecosystem resulting in the loss of phytoplankton diversity in ecological time. The paradox is enhanced under local interactions, indicating that the limited dispersal of phytoplankton reduces interspecific competition greatly. Thus, the paradox of enrichment appears when eutrophication destroys an ecosystem either by elevated interspecific competition within a trophic level and/or destabilization by trophic interactions. Unless eutrophication due to human activities is ceased, the worlds aquatic ecosystems will be at risk.
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A Distinct Human CD4+ T Cell Subset That Secretes CXCL13 in Rheumatoid Synovium.
Arthritis Rheum.
PUBLISHED: 03-18-2013
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A subset of CD4+ T cells in the synovium of patients with rheumatoid arthritis (RA) produce CXCL13, a chemokine that is crucial for the formation of germinal centers. This study was undertaken to determine the relevance of this population to known subsets of T helper cells and to proinflammatory cytokines, and how these cells are generated.
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3D in vivo femoro-tibial kinematics of tri-condylar total knee arthroplasty during kneeling activities.
Knee
PUBLISHED: 03-16-2013
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Kneeling position can serve as an important posture, providing stability and balance from a standing position to sitting on the floor or vice-versa. The purpose of the current study was to determine the kinematics during kneeling activities after subjects were implanted with a tri-condylar total knee arthroplasty.
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Three groups in the 28 joints for rheumatoid arthritis synovitis--analysis using more than 17,000 assessments in the KURAMA database.
PLoS ONE
PUBLISHED: 02-12-2013
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Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis.
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Reduction of Atlantoaxial Subluxation Causes Airway Stenosis.
Spine
PUBLISHED: 02-09-2013
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ABSTRACT: Study Design. A cross-sectional study.Objective. The purpose of this study was to investigate the effect of reduction of anterior atlantoaxial subluxation (AAS) on the oropharyngeal airway space.Summary of Background Data. Our previous studies have shown that reduction of the occipito-C2 angle (O-C2A) makes the mandible shift posteriorly, resulting in oropharyngeal airway stenosis, which occasionally causes postoperative dysphagia after occipito-cervical fusion. Based on this background, we hypothesized that reduction of AAS would also cause oropharyngeal airway stenosis independent of the O-C2A, because it also shifts the mandible posteriorly. To our knowledge, there are no data demonstrating an association between reduction of AAS and the oropharyngeal airway space.Methods. The authors prospectively evaluated 64 patients with rheumatoid arthritis. We analyzed lateral cervical plain X-rays of five different positions (neutral, flexion, extension, retraction, and protrusion), and measured the O-C2A, C2-C6 angle, anterior atlantodental interval (AADI), anteroposterior distance of the narrowest oropharyngeal airway space (nPAS), and so on. The subjects were classified into two groups: group R comprised patients with a "reducible AAS" in dynamic cervical movement, and group N comprised "non-AAS" patients.Results. In the multiple regression analysis, the change in the O-C2A (dOC2A) was the only significant independent variable related to the percentage change in the nPAS from the neutral position (%dnPAS) in group N. On the contrary, the change in the AADI and dOC2A were significantly related to the%dnPAS in group R. No cases in group N and 7 cases (28%) in group R showed a paradoxical decrease in the nPAS in extension, in which the O-C2A is largest and reduction of AAS is obtained.Conclusions. Reduction of AAS has a negative effect on the oropharyngeal airway space. Therefore, reduction of AAS during occipito-cervical fusion may cause postoperative dysphagia despite maintenance of the O-C2A.
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Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis.
PLoS ONE
PUBLISHED: 01-01-2013
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MicroRNAs (miRNAs) are present in human plasma and known as a non-invasive biomarker for cancer detection. Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma samples from three RA patients and three healthy controls (HCs). Plasma miRNAs with more than four times change or with significant (P<0.05) change in expression, or detectable only in RA plasma, were confirmed with plasma from eight RA patients and eight HCs using real-time quantitative PCR. Consistently detectable miRNAs that were significantly different between RA patients and HCs were chosen for further validation with 102 RA patients and 104 HCs. The area under curves (AUC) were calculated after plotting the receiver operating characteristic (ROC) curves. To determine if these miRNAs are specific for RA, the concentrations of these miRNAs were analyzed in 24 patients with osteoarthritis (OA), and 11 patients with systemic lupus erythematosus (SLE). The array analysis and the subsequent confirmation in larger patient cohort identified significant alterations in plasma levels of seven miRNAs. The highest AUC was found for miR-125a-5p, followed in order by miR-24 and miR-26a. Multivariable logistic regression analysis showed that miR-24, miR-30a-5p, and miR-125a-5p were crucial factors for making detection model of RA and provided a formula for Estimated Probability of RA by plasma MiRNA (ePRAM), employing miR-24, miR-30a-5p and miR-125a-5p, which showed increased diagnostic accuracy (AUC: 0.89). The level of miR-24, miR-125a-5p, and ePRAM in OA and SLE patients were lower than that in RA. There was no significant difference in detection for anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients. These results suggest that the plasma concentrations of miR-24 and miR-125a-5p, and ePRAM are potential diagnostic markers of RA even if patients were ACPA-negative.
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Lectin-like oxidized low-density lipoprotein receptor 1 signal is a potent biomarker and therapeutic target for human rheumatoid arthritis.
Arthritis Rheum.
PUBLISHED: 11-10-2011
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To determine whether lectin-like oxidized low-density lipoprotein (ox-LDL) receptor 1 (LOX-1) and the soluble form of LOX-1 (sLOX-1) are novel target molecules for the diagnosis and treatment of rheumatoid arthritis (RA).
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Objective assessment of abnormal gait in patients with rheumatoid arthritis using a smartphone.
Rheumatol. Int.
PUBLISHED: 08-02-2011
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A disturbance in gait pattern is a serious problem in patients with rheumatoid arthritis (RA). The aim of the present study was to examine the utility of the smartphone gait analysis application in patients with RA. The smartphone gait analysis application was used to assess 39 patients with RA (age 65.9 ± 10.0 years, disease duration 11.9 ± 9.4 years) and age-matched control individuals (mean age, 69.1 ± 5.8 years). For all RA patients, the following data were obtained: disease activity score (DAS) 28, modified health assessment questionnaire (mHAQ), and assessment of walking ability. Patients walked 20 m at their preferred speed, and trunk acceleration was measured using a Smartphone. After signal processing, we calculated the following gait parameters for each measurement terminal: peak frequency (PF), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. The gait parameters of RA and control groups were compared to examine the comparability of the 2 groups. Criterion-related validity was determined by evaluating the correlation between gait parameters and clinical parameters using Spearmans correlation coefficient. The RA group showed significantly lower scores for the walking speed, AC, and CV than the control group. There were no significant differences in PF. PF (gait cycle) was mildly associated with gait speed (P < 0.05). AC (gait balance) was moderately associated with the DAS, mHAQ, gait ability, and gait speed (P < 0.05). CV (gait variability) was moderately associated with the DAS, gait ability, and gait speed (P < 0.05). This is the first study to examine the use of a smartphone device for gait pattern measurement. The results suggest that some gait parameters recorded using the smartphone represent an acceptable assessment tool for gait in patients with RA.
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IL-27-producing CD14(+) cells infiltrate inflamed joints of rheumatoid arthritis and regulate inflammation and chemotactic migration.
Cytokine
PUBLISHED: 03-22-2011
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Interleukin (IL)-27, a heterodimeric cytokine, has been reported to be involved in the pathogenesis of autoimmune diseases through mediating differentiation of Th1 or Th17 cells and immune cell activity or survival. However, the origin and effects of IL-27 in joints of rheumatoid arthritis (RA) remain unclear. In this study, we investigated the distribution and anti-inflammatory roles of IL-27 in RA synovium. The IL-27 levels in plasma of RA patients, osteoarthritis (OA) patients, or healthy volunteers (n=15 per group) were equivalent and were at most 1 ng/ml, but the IL-27 level in synovial fluid of RA patients (n=15, mean 0.13 ng/ml; range 0.017-0.37 ng/ml) was significantly higher than that in synovial fluid of OA patients (n=15, mean 0.003 ng/ml; range 0-0.033 ng/ml) and potentially lower than in plasma. We analyzed the protein level of IL-27 produced by RA fibroblast-like synoviocytes (FLSs) or mononuclear cells (MNCs) from RA or OA synovial fluid or peripheral blood and showed that IL-27 in RA joints was derived from MNCs but not from FLSs. We also found by flow cytometry that IL-27-producing MNCs were CD14(+), and that these CD14(+)IL-27(+) cells were clearly detected in RA synovium but rarely in OA synovium by immunohistochemistry. Furthermore, we demonstrated that a relatively physiological concentration of IL-27 below 10 ng/ml suppressed the production of IL-6 and CCL20 from RA FLSs induced by proinflammatory cytokines through the IL-27/IL-27R axis. In the synovial fluid of RA, the IL-27 level interestingly had positive correlation with the IFN-? level (r=0.56, p=0.03), but weak negative correlation with the IL-17A level (r=-0.30, p=0.27), implying that IL-27 in inflammatory joints of RA induces Th1 differentiation and suppresses the development or the migration of Th17 cells. These findings indicate that circulating IL-27-producing CD14(+) cells significantly infiltrate into inflamed regions such as RA synovium and have anti-inflammatory effects in several ways: both directly through the reduction of IL-6 production, and possibly through the induction of Th1 development and the suppression of Th17 development; and indirectly by regulation of recruitment of CCR6(+) cells, such as Th17 cells, through the suppression of CCL20 production. Our results suggest that such a serial negative feedback system could be applied to RA therapy.
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Mechanical implant failure in posterior cervical spine fusion.
Eur Spine J
PUBLISHED: 03-08-2011
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The aim of this study was to determine whether the recent refinement and downsizing of the implants for posterior cervical fusion increase the occurrence of implant failure.
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Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38.
J. Orthop. Res.
PUBLISHED: 04-06-2010
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We investigated the effects of hyaluronan (HA) on interleukin-1? (IL-1?)-stimulated matrix metalloproteinase (MMP)-13 production in human chondrocytes from patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Secreted levels of MMP-13 in conditioned media were detected by immunoblotting, while intracellular MMP-13 synthesis in articular cartilage was evaluated by immunofluorescence microscopic analysis. Mitogen-activated protein kinases (MAPKs), p38, extracellular signal-regulated kinases (ERK), and c-jun NH2-terminal kinase (JNK) were assessed by Western blotting. IL-1? (2?ng/ml) stimulates the secretion of MMP-13 in both OA and RA chondrocytes. Inhibition studies using specific MAPK inhibitors revealed that IL-1? induced MMP-13 via p38 in both OA and RA chondrocytes. HA down-regulates IL-1?-stimulated MMP-13 and phosphorylated p38 (p-p38) in a dose-dependent manner (0.1, 1, 2, and 4?mg/ml). When used at 4?mg/ml, HA inhibits p-p38 phosphorylation by more than 60%. In response to IL-1?, RA chondrocytes express a higher level of p-p38 than that of OA chondrocytes. Inhibition of CD44, using a blocking antibody, significantly reversed the inhibitory effect of HA on both MMP-13 and p-p38. Our study clearly shows that HA inhibits IL-1?-induced MMP-13 via its principal receptor, CD44, and subsequent intracellular p38 MAPK signaling in OA and RA chondrocytes.
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Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis.
Arthritis Res. Ther.
PUBLISHED: 03-28-2010
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MicroRNAs (miRNAs), endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes, are present in human plasma in a stable form. In this study, we investigated whether miRNAs are also stably present in synovial fluids and whether plasma and synovial fluid miRNAs could be biomarkers of rheumatoid arthritis (RA) and osteoarthritis (OA).
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The Bi-Surface total knee arthroplasty: minimum 10-year follow-up study.
Knee
PUBLISHED: 02-23-2010
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The Bi-Surface Knee System (Japan Medical Material, Kyoto, Japan), which has a unique ball-and-socket joint and whose femoral component is made from alumina ceramic, was designed to improve deep knee flexion and long-term durability after total knee arthroplasty. The purpose of this study was to review the clinical results of a minimum 10-year follow-up. Between 1989 and 1997, 507 total knee arthroplasties were carried out in 371 patients. Forty three patients (56 knees) were lost to follow-up. The mean age of the patients at operation was 68.5 years, and the patients were followed up for a mean of 11.7 years. The knees were evaluated on the basis of Knee Society knee score and functional score, radiographs, and Kaplan-Meier survivorship analysis. The knee score was improved from 38.9+/-17.4 points preoperatively to 93.3+/-7.8 points at the latest follow-up (p<0.001). The functional score was improved from 34.9+/-19.3 points to 52.7+/-24.1 points (p<0.001). The mean range of flexion was improved from 118.7+/-21.7 degrees to 124.2+/-20.8 degrees (p<0.001). The critical angle, which means the border to gain more range of flexion postoperatively, was 130.1 degrees. Kaplan-Meier survivorship at 10-year was 95.9% with any operation or radiographic failure as the end point. The corresponding rate was 97.4% with revision of any component as the end point. No ceramic component fracture occurred. The present study demonstrates that good range of flexion was maintained for a long time after total knee arthroplasty with excellent durability. The Bi-Surface Knee System appears to have achieved its design objectives.
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Chemokines in mesenchymal stem cell therapy for bone repair: a novel concept of recruiting mesenchymal stem cells and the possible cell sources.
Mod Rheumatol
PUBLISHED: 01-08-2010
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Skeletal injury is one of the most prevalent clinical problems that jeopardize the activities of daily life, especially in our aging society. Mesenchymal stem cells (MSCs) play pivotal roles in regenerating bones after bone injury. MSCs come from the surrounding tissues and/or circulation. Cell sources may be the bone marrow, periosteum, vessel walls, muscle, circulation, and elsewhere, and the migration of MSCs is necessary for bone healing. The mechanism(s) of recruitment and crucial molecules for cell migration are still unclear, but chemokines and their receptors seem to play critical roles. The induction of MSC recruitment from surrounding tissues or from the circulation can be a helpful modality to induce or to support cell-based therapy for bone regeneration.
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Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis.
Arthritis Rheum.
PUBLISHED: 08-01-2009
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Although interleukin-17 (IL-17)-producing gamma/delta T cells were reported to play pathogenic roles in collagen-induced arthritis (CIA), their characteristics remain unknown. The aim of this study was to clarify whether gamma/delta T cells or CD4+ T cells are the predominant IL-17-producing cells, and to determine what stimulates gamma/delta T cells to secret IL-17 in mice with CIA. The involvement of IL-17-producing gamma/delta T cells in SKG mice with autoimmune arthritis and patients with rheumatoid arthritis (RA) was also investigated.
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CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6+ mononuclear cells and enhances the production of IL-6.
Cytokine
PUBLISHED: 03-28-2009
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Although a notable amount of CCL20 is detectable in the synovial fluid of human rheumatoid arthritis (RA), its role in the pathogenesis of RA remains to be determined. IL-1beta vigorously induced the production of CCL20 from FLSs of human RA and the production of CCL20 induced by TNF-alpha was partially attributed to a trace amount of IL-1beta induced by TNF-alpha. Although IL-6 failed to induce CCL20, TNF-alpha-induced IL-6 enhanced the production of CCL20 in an autocrine/paracrine manner. To determine the role of CCL20 and its sole receptor CCR6 in the recruitment of mononuclear cells (MNCs) into the inflamed joint of RA, conditioned medium of IL-1beta-stimulated FLSs was used in migration assays. The conditioned medium significantly recruited CCR6(+) MNCs in a CCL20-dependent manner. The production of CCL20 induced by TNF-alpha and IL-1beta was modified by helper-T-cell-derived cytokines. Interestingly, CCL20 enhanced the production of IL-6 coordinately with the stimulation of IL-17 but not with that of IFN-gamma. These findings imply FLSs stimulated by proinflammatory cytokines recruit CCR6(+) MNCs including IL-17-producing-helper T cells into the inflamed joint, leading to the enhancement of the production of CCL20, which chemokine and IL-17 coordinately induce proinflammatory cytokines.
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Severe erosive arthropathy requiring surgical treatments in systemic lupus erythematosus.
Mod Rheumatol
PUBLISHED: 03-17-2009
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We report a case of 43-year-old woman with an overlap syndrome of systemic lupus erythematosus (SLE) and dermatomyositis who developed erosive arthritis with extracapsular cysts involving multiple joints. An extensive synovectomy for the left wrist joint and a total joint replacement for the right hip joint were required to achieve complete symptom relief. She was not diagnosed with rheumatoid arthritis (RA). This was a rare case of SLE manifesting non-RA erosive arthritis that required surgical interventions.
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Subaxial subluxation after atlantoaxial transarticular screw fixation in rheumatoid patients.
Eur Spine J
PUBLISHED: 03-12-2009
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The most common cervical abnormality associated with rheumatoid arthritis (RA) is atlantoaxial subluxation, and atlantoaxial transarticular screw fixation has proved to be one of the most reliable, stable fixation techniques for treating atlantoaxial subluxation. Following C1-C2 fixation, however, subaxial subluxation reportedly can bring about neurological deterioration and require secondary operative interventions. Rheumatoid patients appear to have a higher risk, but there has been no systematic comparison between rheumatoid and non-rheumatoid patients. Contributing radiological factors to the subluxation have also not been evaluated. The objective of this study was to evaluate subaxial subluxation after atlantoaxial transarticular screw fixation in patients with and without RA and to find contributing factors. Forty-three patients who submitted to atlantoaxial transarticular screw fixation without any concomitant operation were followed up for more than 1 year. Subaxial subluxation and related radiological factors were evaluated by functional X-ray measurements. Statistical analyses showed that aggravations of subluxation of 2.5 mm or greater were more likely to occur in RA patients than in non-RA patients over an average of 4.2 years of follow-up, and postoperative subluxation occurred in the anterior direction in the upper cervical spine. X-ray evaluations revealed that such patients had a significantly smaller postoperative C2-C7 angle, and that the postoperative AA angle correlated negatively with this. Furthermore, anterior subluxation aggravation was significantly correlated with the perioperative atlantoaxial and C2-C7 angle changes, and these two changes were strongly correlated to each other. In conclusion, after atlantoaxial transarticular screw fixation, rheumatoid patients have a greater risk of developing subaxial subluxations. The increase of the atlantoaxial angel at the operation can lead to a decrease in the C2-C7 angle, followed by anterior subluxation of the upper cervical spine and possibly neurological deterioration.
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Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model.
Arthritis Rheum.
PUBLISHED: 02-28-2009
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Stromal cell-derived factor 1 (SDF-1; CXCL12/pre-B cell growth-stimulating factor) is a dominant chemokine in bone marrow and is known to be involved in inflammatory diseases, including rheumatoid arthritis. However, its role in bone repair remains unknown. The purpose of this study was to investigate the role of SDF-1 and its receptor, CXCR4, in bone healing.
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Biological activation of bone-related biomaterials by recombinant adeno-associated virus vector.
J. Orthop. Res.
PUBLISHED: 02-27-2009
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Gene therapy is a promising clinical tool that is no longer limited as a method to supplement genetic deficits, but rather is considered reliable for delivering proteins to specific tissues or cells. Recombinant adeno-associated virus (rAAV) vector is one of the most potent gene transfer vehicles. Many biomaterials have been used in reconstructive surgery, but their biological inactivity has limited their use. To overcome shortcomings of available bone-related biomaterials, we investigated the combination of rAAV with biomaterials. Taking advantage of the method of lyophilizing rAAV onto biomaterials, we showed that an rAAV coating successfully induced beta-galactosidase protein expression by rat fibroblasts on hydroxyapatite, beta-tricalcium phosphate, and titanium alloy in vitro. beta-Galactosidase expression was detected for 8 weeks after implantation of rAAV-coated hydroxyapatite into rat back muscles in vivo. A coating of bone morphogenetic protein-2-expressing rAAV induced significant de novo bone formation on hydroxyapatite in rat back muscles. Our study demonstrates that the combination of lyophilized rAAV and biomaterials presents a promising strategy for bone regenerative medicine.
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Manufacturers affect clinical results of THA with zirconia heads: a systematic review.
Clin. Orthop. Relat. Res.
PUBLISHED: 01-08-2009
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In the 1980s, zirconia was introduced for THA with the expectation of lower polyethylene wear and better clinical results. However, several studies have reported poor survivorship of zirconia-polyethylene THA. We performed a systematic review and meta-analysis of zirconia-polyethylene THA to confirm or refute the theoretical advantages of this combination. Of 163 studies identified by a comprehensive search, seven met our selection criteria. These involved 769 hips of 586 patients with a mean age of 56.8 years and a minimum followup of 60 months (mean, 89.2 months; range, 60-155 months). The consolidated revision rate of zirconia-polyethylene THA at 89.2 months was higher than that of nonzirconia-polyethylene THA by 5% (risk difference, 0.05; 95% confidence interval, 0.02-0.08). Subgroup meta-analysis suggested THAs with zirconia heads from Ceraver had more revision surgery than nonzirconia heads (risk difference, 0.08; 95% confidence interval, 0.03-0.14), whereas zirconia heads from DePuy did not (risk difference, 0.02; 95% confidence interval, -0.01-0.06). The meta-analysis for annual linear polyethylene wear (which did not involve zirconia heads from Ceraver because of insufficient descriptions) showed no difference between zirconia and control groups. Collectively, THAs with high-quality zirconia heads appear to have prosthesis survivorship and polyethylene wear equivalent to those of THAs with traditional materials, but differing quality among zirconia heads could lead to poor survivorship of prostheses.
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Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.
PLoS ONE
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Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF) plays important roles in the biological and physiological functions of haematopoietic and mesenchymal stem cells. This chemokine regulates the formation of multiple organ systems during embryogenesis. However, its roles in skeletal development remain unclear. Here we investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic chondrocytes in the newly formed endochondral callus of rib fracture as well as in the growth plate of normal mouse tibia by immunohistochemical analysis. Using SDF-1(-/-) mouse embryo, we histologically showed that the total length of the whole humeri of SDF-1(-/-) mice was significantly shorter than that of wild-type mice, which was contributed mainly by shorter hypertrophic and calcified zones in SDF-1(-/-) mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/-) mouse humeri showed less F-actin and rounder shape than that of wild-type mice. Primary chondrocytes from SDF-1(-/-) mice showed the enhanced formation of philopodia and loss of F-actin. The administration of SDF-1 to primary chondrocytes of wild-type mice and SDF-1(-/-) mice promoted the formation of actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/-) mice showed the growth delay, which was recovered by an exogenous administration of SDF-1. mRNA expression of type X collagen in metatarsals and in primary chondrocytes of SDF-1(-/-) mouse embryo was down-regulated while the administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1 regulates the actin organization and stimulates bone growth by mediating chondrocyte hypertrophy.
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Reliability and validity of gait analysis by android-based smartphone.
Telemed J E Health
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Smartphones are very common devices in daily life that have a built-in tri-axial accelerometer. Similar to previously developed accelerometers, smartphones can be used to assess gait patterns. However, few gait analyses have been performed using smartphones, and their reliability and validity have not been evaluated yet. The purpose of this study was to evaluate the reliability and validity of a smartphone accelerometer. Thirty healthy young adults participated in this study. They walked 20 m at their preferred speeds, and their trunk accelerations were measured using a smartphone and a tri-axial accelerometer that was secured over the L3 spinous process. We developed a gait analysis application and installed it in the smartphone to measure the acceleration. After signal processing, we calculated the gait parameters of each measurement terminal: peak frequency (PF), root mean square (RMS), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. Remarkable consistency was observed in the test-retest reliability of all the gait parameter results obtained by the smartphone (p<0.001). All the gait parameter results obtained by the smartphone showed statistically significant and considerable correlations with the same parameter results obtained by the tri-axial accelerometer (PF r=0.99, RMS r=0.89, AC r=0.85, CV r=0.82; p<0.01). Our study indicates that the smartphone with gait analysis application used in this study has the capacity to quantify gait parameters with a degree of accuracy that is comparable to that of the tri-axial accelerometer.
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The carboxyl-terminal region of Crtac1B/LOTUS acts as a functional domain in endogenous antagonism to Nogo receptor-1.
Biochem. Biophys. Res. Commun.
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Myelin-derived axon growth inhibitors, such as Nogo, bind to Nogo receptor-1 (NgR1) and thereby limit the action of axonal regeneration after injury in the adult central nervous system. Recently, we have found that cartilage acidic protein-1B (Crtac1B)/lateral olfactory tract usher substance (LOTUS) binds to NgR1 and functions as an endogenous NgR1 antagonist. To examine the functional domain of LOTUS in the antagonism to NgR1, analysis using the deletion mutants of LOTUS was performed and revealed that the carboxyl-terminal region (UA/EC domain) of LOTUS bound to NgR1. The UA/EC fragment of LOTUS overexpressed together with NgR1 in COS7 cells abolished the binding of Nogo66 to NgR1. Overexpression of the UA/EC fragment in cultured chick dorsal root ganglion neurons suppressed Nogo66-induced growth cone collapse. These findings suggest that the UA/EC region is a functional domain of LOTUS serving for an antagonistic action to NgR1.
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Inhibition of miR-92a enhances fracture healing via promoting angiogenesis in a model of stabilized fracture in young mice.
J. Bone Miner. Res.
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MicroRNAs (miRNAs) are endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes. Although no miRNA has been reported to play an important role in the regulation of fracture healing, several miRNAs control key elements in tissue repair processes such as inflammation, hypoxia response, angiogenesis, and stem cell differentiation including osteogenesis and chondrogenesis. We compared the plasma concentrations of 134 miRNAs in four patients with trochanteric fractures and four healthy controls (HCs), and the levels of six miRNAs were dysregulated. Among these miRNAs, miR-92a levels were significantly decreased after 24 hours following fracture, compared to HCs. In patients with a trochanteric fracture or a lumbar compression fracture, the plasma concentrations of miR-92a were lower on days 7 and 14, but had recovered on day 21 after the surgery or injury. To determine whether systemic downregulation of miR-92a can modulate fracture healing, we administered antimir-92a, designed using locked nucleic acid technology to inhibit miR-92a, to mice with a femoral fracture. Systemic administration of antimir-92a twice a week increased the callus volume and enhanced fracture healing. Enhancement of fracture healing was also observed after local administration of antimir-92a. Neovascularization was increased in mice treated with antimir-92a. These results suggest that plasma miR-92a plays a crucial role in bone fracture healing in human and that inhibition of miR-92a enhances fracture healing through angiogenesis and has therapeutic potential for bone repair.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.