Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis

Abstract

There is currently no effective medical treatment for temporomandibular joint osteoarthritis (TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β (TGF-β) signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder (TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease (CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by µCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen (Col X), p-Smad2/3a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-β signalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.

Osteoarthritis: growth factor signalling drives degeneration of jaw joint

Blocking the activity of a critical growth factor could help treat degenerative disease of the jaw joint, according to experiments in three rodent models. Xuedong Zhou from Sichuan University in Chengdu, China, examined the cartilage and adjoining layer of bone found at the ends of the jawbone in a rat model of temporomandibular joint disorder and in two related mouse models. In all three, the researchers observed tissue abnormalities consistent with what’s seen in humans with osteoarthritis of the jaw joint, a condition with no effective therapeutic options. They showed that transforming growth factor-β, a master regulatory protein, displayed aberrant signalling patterns in these tissues and that blocking this protein’s receptor with a drug attenuated the disease process. The findings help explain what drives jaw joint osteoarthritis — and point to a strategy for treating it.

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Funding

National Key Research and Development Program of China 2016YFC1102700(X.Z)

Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)(2016JQ0054)