generation-hypoparathyroid-rats-via-carbon-nanoparticle-assisted

Generation of Hypoparathyroid Rats <em>via</em> Carbon-Nanoparticle-Assisted Parathyroidectomy

Hypoparathyroidism (HypoPT) is a rare disease involving the parathyroid glands that is characterized by a reduced secretion or potency of the parathyroid ...

Sichuan University

West China Hospital of Stomatology

Osteoarthritis (OA) is a chronic degenerative joint disease and the major cause of joint pain and disability in the elderly. It is mainly characterized by articular cartilage degradation and subchondral bone remodeling. There are two main types of OA: natural occurring OA and secondary OA, mainly associated with aging and trauma, respectively. In this study, we established two OA models in rat knee joints to simulate the two types of OA, using the type II collagenase injection (CI) and anterior cruciate ligament transection (ACLT), respectively. After intervention for 2-6 weeks, cartilage and subchondral bone changes were detected in histological staining, immunochemistry, and micro-CT. Results showed that both models with typical pathology changes of OA were successfully induced, while the development and severity of OA process in the models were different. In ACLT rats, the cartilage damage was milder, lasted for a shorter time, and subchondral bone reconstruction occurred earlier, compared with the changes in CI rats. The cartilage damage was secondary to subchondral bone change in ACLT rats, while subchondral bone change was secondary to cartilage degeneration in CI rats. In conclusion, the interaction between cartilage and subchondral bone is different between the natural-occurring and secondary OA models. These two models not only suggest potential different mechanisms of the two types of OA, but also provide new directions for OA treatment and prevention.

Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models.

Ionizing radiation (IR)-induced vascular disorders slow down tissue regeneration. Exosomes derived from plasma exhibit potential to promote angiogenesis; meanwhile, the immune microenvironment plays a significant role in the process. This study aimed to test the hypothesis that plasma exosomes promote angiogenesis in irradiated tissue by mediating the immune microenvironment. First, we explored the impact of IR on macrophages. We found that cell viability and capacity for promoting angiogenesis were decreased in irradiated macrophages compared to control macrophages. Then, we isolated and characterized rat plasma-derived exosomes (RP-Exos) which were defined as 40-160 nm extracellular vesicles extracted from rat plasma. Afterward, we evaluated the effects of RP-Exos on the behaviors of irradiated macrophages. Our results show that RP-Exos promoted cell proliferation. More importantly, we found that RP-Exos stimulated the immune microenvironment in a manner that improved the angiogenesis-related genes and proteins of irradiated macrophages. The supernatant of macrophage cell cultures was used as conditioned medium to treat human primary umbilical vein endothelial cells, further confirming the pro-angiogenic ability of macrophages receiving RP-Exo intervention. RP-Exos were used in vivo to treat irradiated skin or calvarial defects in irradiated Sprague-Dawley male rats. The results indicated the ability of RP-Exos to enhance angiogenesis and promote tissue regeneration. Our research suggested the potential of plasma exosomes to be used as immunomodulatory agents with angiogenic capacity to treat radiation-associated vascular disorders and facilitate tissue repair.

Exosomes derived from plasma: promising immunomodulatory agents for promoting angiogenesis to treat radiation-induced vascular dysfunction.

Temporomandibular disorders (TMD) are diseases involving the temporomandibular joint (TMJ), masticatory muscles, and osseous components. TMD has a high prevalence, with an estimated 4.8% of the U.S. population experiencing signs and symptoms, and represents a financial burden to both individuals and society. During TMD progression, the most frequently affected site is the condylar cartilage. Comprising both fibrous and cartilaginous tissues, condylar cartilage has restricted cell numbers but lacks a vascular supply and has limited regenerative properties. In 2016, a novel stem cell niche containing a reservoir of fibrocartilage stem cells (FCSCs) was discovered in the condylar cartilage of rats. Subsequently, FCSCs were identified in mouse, rabbit, and human condylar cartilage. Unlike mesenchymal stem cells or other tissue-specific stem/progenitor cells, FCSCs play a unique role in the development and regeneration of fibrocartilage. More importantly, engraftment treatment of FCSCs has been successfully applied in animal models of TMD. In this context, FCSCs play a major role in the regeneration of newly formed cartilage. Furthermore, FCSCs participate in the regeneration of intramembranous bone by interacting with endothelial cells in bone defects. This evidence highlights the potential of FCSCs as an ideal stem cell source for the regeneration of oral maxillofacial tissue. This review is intended to detail the current knowledge of the characteristics and function of FCSCs in the TMJ, as well as the potential therapeutic applications of FCSCs. A deep understanding of the properties of FCSCs can thus inform the development of promising, biologically based strategies for TMD in the future.

Fibrocartilage Stem Cells in the Temporomandibular Joint: Insights From Animal and Human Studies.

Dental follicle progenitor/stem cells (DFPCs) are a group of dental mesenchyme stem cells that lie in the dental follicle and play a critical role in tooth development and maintaining function. Originating from neural crest, DFPCs harbor a multipotential differentiation capacity. More importantly, they have superiorities, including the easy accessibility and abundant sources, active self-renewal ability and noncontroversial sources compared with other stem cells, making them an attractive candidate in the field of tissue engineering. Recent advances highlight the excellent properties of DFPCs in regeneration of orofacial tissues, including alveolar bone repair, periodontium regeneration and bio-root complex formation. Furthermore, they play a unique role in maintaining a favorable microenvironment for stem cells, immunomodulation and nervous related tissue regeneration. This review is intended to summarize the current knowledge of DFPCs, including their stem cell properties, physiological functions and clinical application potential. A deep understanding of DFPCs can thus inspire novel perspectives in regenerative medicine in the future.

Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications.

Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) are two peptides that regulate mineral ion homeostasis, skeletal development, and bone turnover by activating parathyroid hormone 1 receptor (PTH1R). PTH1R signaling is of profound clinical interest for its potential to stimulate bone formation and regeneration. Recent pre-clinical animal studies and clinical trials have investigated the effects of PTH and PTHrP analogs in the orofacial region. Dental mesenchymal stem cells (MSCs) are targets of PTH1R signaling and have long been known as major factors in tissue repair and regeneration. Previous studies have begun to reveal important roles for PTH1R signaling in modulating the proliferation and differentiation of MSCs in the orofacial region. A better understanding of the molecular networks and underlying mechanisms for modulating MSCs in dental diseases will pave the way for the therapeutic applications of PTH and PTHrP in the future. Here we review recent studies involving dental MSCs, focusing on relationships with PTH1R. We also summarize recent basic and clinical observations of PTH and PTHrP treatment to help understand their use in MSCs-based dental and bone regeneration.

Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications.

To summarize unfavorable fracture patterns during sagittal split ramus osteotomy (SSRO) and investigate the association with influencing factors.

Risk Factors Analysis for Different Types of Unfavorable Fracture Patterns During Sagittal Split Ramus Osteotomy: A Retrospective Study of 2008 Sides.

Hydrogels with high mechanical strength and injectability have attracted extensive attention in biomedical and tissue engineering. However, endowing a hydrogel with both properties is challenging because they are generally inversely related. In this work, by constructing a multi-hydrogen-bonding system, a high-strength and injectable supramolecular hydrogel is successfully fabricated. It is constructed by the self-assembly of a monomeric nucleoside molecular gelator (2-amino-2'-fluoro-2'-deoxyadenosine (2-FA)) with distilled water/phosphate buffered saline as solvent. Its storage modulus reaches 1 MPa at a concentration of 5.0 wt%, which is the strongest supramolecular hydrogel comprising an ultralow-molecular-weight (MW < 300) gelator. Furthermore, it exhibits excellent shear-thinning injectability, and completes the sol-gel transition in seconds after injection at 37 °C. The multi-hydrogen-bonding system is essentially based on the synergistic interactions between the double NH groups, water molecules, and 2'-F atoms. Furthermore, the 2-FA hydrogel exhibits excellent biocompatibility and antibacterial activity. When applied to rat molar extraction sockets, compared to natural healing and the commercial hemorrhage agent gelatin sponge, the 2-FA hydrogel exhibits faster degradation and induces less osteoclastic activity and inflammatory infiltration, resulting in more complete bone healing. In summary, this study provides ideas for proposing a multifunctional, high-strength, and injectable supramolecular hydrogel for various biomedical engineering applications.

High-Strength and Injectable Supramolecular Hydrogel Self-Assembled by Monomeric Nucleoside for Tooth-Extraction Wound Healing.

Mature vasculature is important for the survival of bioengineered tissue constructs, both  and ; however, the fabrication of fully vascularized tissue constructs remains a great challenge in tissue engineering. Indirect three-dimensional (3D) bioprinting refers to a 3D printing technique that can rapidly fabricate scaffolds with controllable internal pores, cavities, and channels through the use of sacrificial molds. It has attracted much attention in recent years owing to its ability to create complex vascular network-like channels through thick tissue constructs while maintaining endothelial cell activity. Biodegradable materials play a crucial role in tissue engineering. Scaffolds made of biodegradable materials act as temporary templates, interact with cells, integrate with native tissues, and affect the results of tissue remodeling. Biodegradable ink selection, especially the choice of scaffold and sacrificial materials in indirect 3D bioprinting, has been the focus of several recent studies. The major objective of this review is to summarize the basic characteristics of biodegradable materials commonly used in indirect 3D bioprinting for vascularization, and to address recent advances in applying this technique to the vascularization of different tissues. Furthermore, the review describes how indirect 3D bioprinting creates blood vessels and vascularized tissue constructs by introducing the methodology and biodegradable ink selection. With the continuous improvement of biodegradable materials in the future, indirect 3D bioprinting will make further contributions to the development of this field.

Biodegradable Inks in Indirect Three-Dimensional Bioprinting for Tissue Vascularization.

Maxillofacial bone defects are commonly seen in clinical practice. A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration. The fibroblast growth factor (FGF) signalling pathway is critical for the development of maxillofacial bone. Klotho, a type I transmembrane protein, is an important components of FGF receptor complexes. Recent studies have reported the presence of Klotho expression in bone. However, the role of Klotho in cranioskeletal development and repair remains unknown. Here, we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions. Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo. Under conditions of inflammation and trauma-induced bone loss, we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression. More importantly, we show for the first time that Klotho is present in human alveolar bone, with a distinct expression pattern under both normal and pathological conditions. In summary, our results identify the mechanism whereby Klotho expressed in Osx-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair. Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration. It may also be a target for future therapeutics.

Klotho in Osx-mesenchymal progenitors exerts pro-osteogenic and anti-inflammatory effects during mandibular alveolar bone formation and repair.

Poor vascularization was demonstrated as a factor inhibiting bone regeneration in patients receiving radiotherapy. Various copper-containing materials have been reported to increase angiogenesis, therefore might improve bone formation. In this study, a Ti6Al4V-1.5Cu alloy was prepared using selective laser melting (SLM) technology. The immunomodulatory and pro-angiogenic effects of the Ti6Al4V-1.5Cu alloys were examined. In vitro, Ti6Al4V-1.5Cu stimulated vascular formation by restraining inflammatory factors and provoking angiogenic factors in non-irradiated and irradiated macrophages. In vivo, the angiogenic effects of the Ti6Al4V-1.5Cu alloy were confirmed using an irradiated rat femur defect model. Moreover, we found that the biological effects of the Ti6Al4V-1.5Cu alloy were partially due to the release of copper ions and associated with PI3K-Akt signaling pathway. In conclusion, this study indicated the potential of the Ti6Al4V-1.5Cu alloy to promote angiogenesis by releasing copper ions and inhibiting inflammation in normal and irradiated tissues.

Copper-containing titanium alloys promote angiogenesis in irradiated bone through releasing copper ions and regulating immune microenvironment.

Osteochondroma is a common benign skeletal disorder for which different molecular and histological features of long bones have been reported. We investigated cell-of-origin and molecular mechanisms of a rare condylar osteochondroma (CO).

Regulatory role of human fibrocartilage stem cells in condyle osteochondroma.

Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER ; Tm mice and conditional Igf1 deletion using Gli1-/Col2-CreER ; Igf1 mice. In Gli1-CreER ; Tm mice, red fluorescence (RFP ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1 /Col2 cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER ; Igf1 mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1 FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1 -specific deletion of Igf1. In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).

Igf1 Regulates Fibrocartilage Stem Cells, Cartilage Growth, and Homeostasis in the Temporomandibular Joint of Mice.

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11 mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2 non-chondrogenic fibroblasts instead of Chad chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury.

Article	Year
Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models. PeerJ\| PubMed ID: 32341895	2020
Exosomes derived from plasma: promising immunomodulatory agents for promoting angiogenesis to treat radiation-induced vascular dysfunction. PeerJ\| PubMed ID: 33859878	2021
Fibrocartilage Stem Cells in the Temporomandibular Joint: Insights From Animal and Human Studies. Frontiers in cell and developmental biology\| PubMed ID: 33987185	2021
Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications. Biomolecules\| PubMed ID: 34356621	2021
Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications. Frontiers in cell and developmental biology\| PubMed ID: 34760881	2021
Risk Factors Analysis for Different Types of Unfavorable Fracture Patterns During Sagittal Split Ramus Osteotomy: A Retrospective Study of 2008 Sides. Aesthetic plastic surgery\| PubMed ID: 34984494	2022
High-Strength and Injectable Supramolecular Hydrogel Self-Assembled by Monomeric Nucleoside for Tooth-Extraction Wound Healing. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 35066934	2022
Biodegradable Inks in Indirect Three-Dimensional Bioprinting for Tissue Vascularization. Frontiers in bioengineering and biotechnology\| PubMed ID: 35402417	2022
Klotho in Osx-mesenchymal progenitors exerts pro-osteogenic and anti-inflammatory effects during mandibular alveolar bone formation and repair. Signal transduction and targeted therapy\| PubMed ID: 35538062	2022
Copper-containing titanium alloys promote angiogenesis in irradiated bone through releasing copper ions and regulating immune microenvironment. Biomaterials advances\| PubMed ID: 35882157	2022
Regulatory role of human fibrocartilage stem cells in condyle osteochondroma. Cell proliferation\| PubMed ID: 36162830	2023
Igf1 Regulates Fibrocartilage Stem Cells, Cartilage Growth, and Homeostasis in the Temporomandibular Joint of Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research\| PubMed ID: 36722289	2023
A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury. Nature communications\| PubMed ID: 36788226	2023

Peiran Li

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