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.

Parathyroid hormone ameliorates temporomandibular joint osteoarthritic‐like changes related to age

“…Temporomandibular joint samples were harvested at indicated times and scanned using a microCT scanner (μCT50; SCANO, Switzerland) at a voltage of 50 kVp, a current of 200 µA and a resolution of 3.0 µm per pixel. The images were reconstructed and performed three‐dimensional histomorphometry based on a previous report . Briefly, two cubic regions of interest (each 100 × 100 × 100 µm 3 ) were defined from the middle of the centre and posterior third of the condylar subchondral cancellous bone.…”

“…In the mandibular condylar cartilage, ageing causes reduction in chondrocytes number and viability, decrease in matrix synthesis, and the appearance of OA lesions along the articular surface of the joint . In the subchondral bone region, ageing animals exhibited significantly reduced bone volume …”

Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

“…In the early stages of TMJ OA, upregulation of genes involved in osteoclast activity and/or an increase in RANKL/OPG ratio in subchondral bone contributes to an increase in subchondral bone turnover in biglycan/fibromodulin-deficient mice [53]. Osteoblast-specific transforming growth factor (TGF) -β1 transgenic mice in the bone marrow were used to have high levels of active TGF-β1 to assess the effect of overexpressed TGF-β1 on TMJ OA [54]. Through this model, excessive apoptosis of the mandibular chondrocytes, upregulation of MMP-9, MMP-13 and vascular endothelial growth factor (VEGF) in chondrocytes, and decreased bone mineral density were observed.…”

Current Strategies for the Treatment of Early Stage Osteoarthritis

“…Under the circumstance, a novel therapeutic strategy in light of the recently emerging coupling mechanism of bone resorption and formation (Cao, 2011;Wan et al, 2012;Zhen and Cao, 2014;Sims and Martin, 2015;Xie et al, 2016) would be an ideal approach to treat subchondral bone as a target in OA. Many research findings have shown that TGF-β1 and IGF-1 in the bone matrix function to couple bone resorption and formation, and modulation of their activities can be an effective prevention and treatment for OA (Zhen et al, 2013;Xu et al, 2015;Cui et al, 2016;Zheng et al, 2018). Likewise, activity modulations of RANKL and Sema4D in other two cellular communications can also regulate bone resorption and formation.…”