applying-three-dimensional-uniaxial-mechanical-stimulation-bioreactor

Applying a Three-dimensional Uniaxial Mechanical Stimulation Bioreactor System to Induce Tenogenic Differentiation of Tendon-Derived Stem Cells

Tendinopathy is a common chronic tendon disease relating to inflammation and degeneration in an orthopaedic area. With high morbidity, limited ...

University of Western Australia

Osteocytes comprising over 90% of the bone cell population are highly susceptible to the adverse effects of glucocorticoids (GC) administration. Here we observed that Dexamethasone (Dex) induces a robust cytoskeleton rearrangement and decreases Cx43 protein expression in osteocyte-like MLO-Y4 cells. Using a Dmp1Cre-mT/mG osteocyte ex vivo culture system, we found significant shortening of dendritic processes in primary osteocytes following Dex administration. Loss of dendritic processes is a consequence of reduced Cx43 connectivity upon Dex induced autophagy in both RFP-GFP-LC3B transfected MLO-Y4 cells and primary calvarial osteocytes from LC3GFP transgenic mice. Upon the induction of autophagy by Dex, Cx43 was internalized into autophagosome/autolysosomes and degraded by autophagy. The degradation was attenuated following lysosomal inhibition using chloroquine (CLQ) and suppression of autophagy by Atg5 silencing. Inhibition Akt-mTORC1 signaling by Dex induces autophagy subsequently resulting in Cx43 degradation.Activation of Akt phosphorylation by IGF-1 attenuated Dex induced autophagy and degradation of Cx43. Together, we demonstrated that GC impair osteocyte cell-cell connectivity via autophagy mediated degradation of Cx43 through inhibition of the Akt-mTORC1 signaling. This may account for the deleterious effect of GC-induced bone loss. 

Glucocorticoid impairs cell-cell communication by autophagy-mediated degradation of connexin 43 in osteocytes.

Alveolar bone loss is a common problem that affects dental implant placement. A barrier between the bone substitute and gingiva that can prevent fibro-tissue ingrowth, bacterial infection and induce bone formation is a key factor in improving the success of alveolar ridge reconstruction. This study aims to develop a bioactive collagen barrier material for guided bone regeneration, that is coupled with anti-bacterial and anti-inflammatory properties. We have evaluated two silver coating methods and found controllable and precise coating achieved by sonication compared with sputtering. The optimized AgNP-coated collagen membrane exhibited excellent anti-bacterial effects against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with limited cellular toxicity. It also displayed effective anti-inflammatory effects by reducing the expression and release of inflammatory cytokines including IL-6 and TNF-alpha. Additionally, AgNP-coated collagen membranes were able to induce osteogenic differentiation of mesenchymal stem cells that guide bone regeneration. These findings demonstrate the potential application of AgNP-coated collagen membranes to prevent infection after bone graft introduction in alveolar ridge reconstruction.

Fabrication of a silver nanoparticle-coated collagen membrane with anti-bacterial and anti-inflammatory activities for guided bone regeneration.

[This corrects the article DOI: 10.18632/oncotarget.9034.].

Correction: Glucocorticoid impairs cell-cell communication by autophagy-mediated degradation of connexin 43 in osteocytes.

Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA.

Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis.

Obesity-related osteoarthritis (OA) is a complex, multifactorial condition that can cause significant impact on patients' quality of life. Whilst chronic inflammation, adipocytokines and metabolic factors are considered to be important pathogenic factors in obesity related OA, there has been limited investigation into the biomechanical impact of obesity on OA development. This review aims to demonstrate that mechanical factors are the major pathological cause of obesity-related OA. The effect of obesity on pathological changes to the osteochondral unit and surrounding connective tissues in OA is summarized, as well as the impact of obesity-related excessive and abnormal joint loading, concomitant joint malalignment and muscle weakness. An integrated therapeutic strategy based on this multi-factorial presentation is presented, to assist in the management of obesity related OA.

Article	Year
Glucocorticoid impairs cell-cell communication by autophagy-mediated degradation of connexin 43 in osteocytes. Oncotarget\| PubMed ID: 27127181	2016
Fabrication of a silver nanoparticle-coated collagen membrane with anti-bacterial and anti-inflammatory activities for guided bone regeneration. Biomedical materials (Bristol, England)\| PubMed ID: 30213920	2018
Correction: Glucocorticoid impairs cell-cell communication by autophagy-mediated degradation of connexin 43 in osteocytes. Oncotarget\| PubMed ID: 31258851	2019
Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis. Annals of the rheumatic diseases\| PubMed ID: 32269059	2020
Pathogenesis and clinical management of obesity-related knee osteoarthritis: Impact of mechanical loading. Journal of orthopaedic translation\| PubMed ID: 32695606	2020

Lianzhi Chen

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