Aberrant activation of latent transforming growth factor-\u03b2 initiates the onset of temporomandibular joint osteoarthritis

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

doi:10.1038/s41413-018-0027-6

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.

Highlights

The most common degenerative condition observed in temporomandibular joint disorder (TMD) is osteoarthritis (OA), which causes severe pain and discomfort on one or both sides of the face.[1,2]
Its prevalence increases with occlusal disorder, which is characterised by marked changes in the condylar cartilage and altered composition and material properties of the cartilage matrix.[7]
Cartilage degeneration observed in the bone marrow in the TMD group and in ageing in Temporomandibular joint OA (TMJ-OA) is often accompanied by a high Osteoarthritis Research Society International (OARSI) score and mice (60-wk-old mice) than in mice in the respective control groups (Figs. 3c, d)

Summary

INTRODUCTION

The most common degenerative condition observed in temporomandibular joint disorder (TMD) is osteoarthritis (OA), which causes severe pain and discomfort on one or both sides of the face.[1,2] One percent of Hong Kong Chinese individuals have frequent TMD-related jaw pain,[3] and 14.56% of mainland Chinese patients with TMD exhibit radiographic signs of OA.[4]. As secondary cartilage, differs from other cartilaginous tissue It can be distinguished as a fibrous layer, a proliferative cell layer, a chondrocytic cell layer and a hypertrophic cell layer according to the cellular characteristics.[8,9]. Subchondral bone can rescue TMJ-OA progression remains to be mice. The volume of subchondral bone (%, BV/TV) was lower, but the Tb.Sp was higher in CED mice than in WT mice

RESULTS

Findings

MATERIALS AND METHODS