Inhibition of mTORC1 in the rat condyle subchondral bone aggravates osteoarthritis induced by the overly forward extension of the mandible.

The present study aimed to investigate the role of mammalian target of rapamycin complex 1 (mTORC1) in the remodeling of the condyle subchondral bone in rats with temporomandibular joint osteoarthritis (TMJ OA) and explore the mechanisms involved. In this study, we used rats fitted with appliances to overly extend the mandible forward as an animal model of TMJ OA. Bone samples were collected 2, 4, and 8 weeks after appliance fixation. Histological changes in the condyle subchondral bone were assessed by staining with hematoxylin and eosin, safranin O, and tartrate-resistant acid phosphatase. Real-time polymerase chain reaction and immunohistochemical analyses were performed to evaluate the expression levels of osterix, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and mTORC1 in the condyle subchondral bone. The dissected condyles were analyzed using a micro-CT scanner. We also investigated changes in the condyle subchondral bone after mTORC1 pathway inhibition. In the early stages of TMJ OA, preosteoblasts, osteoblasts, and osteoclasts of the condyle subchondral bone were activated, which stimulated subchondral bone loss. MTORC1 was activated in subchondral bone preosteoblasts in rats with TMJ OA. The mTORC1 pathway was inhibited by a local injection of rapamycin, and the number of osteoblasts and mRNA levels of osteogenic markers in the condyle subchondral bone decreased, but the number of osteoclasts was basically unchanged. As a result, in the early stages of TMJ OA, subchondral bone loss and aggravation of OA were observed. These findings suggest that the mTORC1 signaling pathway plays an important role in subchondral bone remodeling during early stages of TMJ OA.