Background: Temporomandibular joint osteoarthritis (TMJOA) seriously affects the health of patients, and the current treatments are invasive and only used for advanced cases. Bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (BMSC-sEVs) may represent a safer and more effective treatment, but their role in TMJOA has not been elucidated. This study attempted to analyze the cartilage reconstruction effect of BMSC-sEVs on TMJOA and the mechanism underlying this effect.

Methods: BMSC-sEVs were isolated and purified by microfiltration and ultrafiltration and were subsequently characterized by nanoparticle tracking analysis, electron microscopy, and immunoblotting. TMJOA models were established in vivo and in vitro, and hematoxylin–eosin staining, immunohistochemistry, and histological scoring were performed to analyze the histological changes in TMJOA cartilage tissues treated with BMSC-sEVs. The proliferation, migratory capacity, and cell cycle distribution of TMJOA cartilage cells treated with BMSC-sEVs were detected. Furthermore, the related mechanisms were studied by bioinformatic analysis, immunoblotting, and quantitative PCR, and they were further analyzed by knockdown and inhibitor techniques.

Results: The acquisition and identification of BMSC-sEVs were efficient and satisfactory. Compared with the osteoarthritis (OA) group, the condylar tissue of the OA group treated with BMSC-sEV (OA^sEV) showed an increase in cartilage lacuna and hypertrophic cartilage cells in the deep area of the bone under the cartilage. Significantly upregulated expression of proliferating cell nuclear antigen and cartilage-forming factors and downregulated expression of cartilage inflammation-related factors in OA^sEV were observed. In addition, we found higher rates of cell proliferation and migratory activity and alleviated G1 stagnation of the cell cycle of OA^sEV. Autotaxin was found in the BMSC-sEVs, and key factors of the Hippo pathway, Yes-associated protein (YAP), phosphorylated Yes-associated protein (p-YAP), etc. were upregulated in the OA^sEV group. Treatment with BMSC-sEVs after autotaxin knockdown or inhibition no longer resulted in expression changes in cartilage-forming and inflammation-related factors and key factors of the Hippo pathway.

Conclusions: These results suggest that the autotaxin–YAP signaling axis plays an important role in the mechanism by which BMSC-sEVs promote cartilage reconstruction in TMJOA, which may provide guidance regarding their therapeutic applications as early and minimally invasive therapies for TMJOA, and provide insight into the internal mechanisms of TMJOA.

Osteochondral lesions (OL) are a common clinical problem for orthopedic surgeons worldwide and are associated with multiple clinical scenarios ranging from trauma to osteonecrosis. OL vary from chondral lesions in that they involve the subchondral bone and chondral surface, making their management more complex than an isolated chondral injury. Subchondral bone involvement allows for a natural healing response from the body as marrow elements are able to come into contact with the defect site. However, this repair is inadequate resulting in fibrous scar tissue. The second differentiating feature of OL is that damage to the subchondral bone has deleterious effects on the mechanical strength and nutritive capabilities to the chondral joint surface. The clinical solution must, therefore, address both the articular cartilage as well as the subchondral bone beneath it to restore and preserve joint health. Both cartilage and subchondral bone have distinctive functional requirements and therefore their physical and biological characteristics are very much dissimilar, yet they must work together as one unit for ideal joint functioning. In the past, the obvious solution was autologous graft transfer, where an osteochondral bone plug was harvested from a non-weight bearing portion of the joint and implanted into the defect site. Allografts have been utilized similarly to eliminate the donor site morbidity associated with autologous techniques and overall results have been good but both techniques have their drawbacks and limitations. Tissue engineering has thus been an attractive option to create multiphasic scaffolds and implants. Biphasic and triphasic implants have been under explored and have both a chondral and subchondral component with an interface between the two to deliver an implant which is biocompatible and emulates the osteochondral unit as a whole. It has been a challenge to develop such implants and many manufacturing techniques have been utilized to bring together two unalike materials and combine them with cellular therapies. We summarize the functions of the osteochondral unit and describe the currently available management techniques under study.