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

Liwei Zheng; Caixia Pi; Jun Zhang; Yi Fan; Chen Cui; Yang Zhou; Jianxun Sun; Quan Yuan; Xin Xu; Ling Ye; Xu Cao; Xuedong Zhou

doi:10.1038/s41413-018-0027-6

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

Bone Res. 2018 Sep 11:6:26. doi: 10.1038/s41413-018-0027-6. eCollection 2018.

Authors

Liwei Zheng^#¹, Caixia Pi^#¹, Jun Zhang^#¹, Yi Fan¹, Chen Cui¹, Yang Zhou¹, Jianxun Sun¹, Quan Yuan¹, Xin Xu¹, Ling Ye¹, Xu Cao², Xuedong Zhou¹

Affiliations

¹ 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
² 2Department of Orthopaedic Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland USA.

^# Contributed equally.

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.