Condylar Changes And MTORC1 Signaling Pathway In Rat Of Functional Mandibular Advancement

Objective:Osteomandibular retraction is mainly manifested as class II malocclusion,which seriously affects the function and aesthetics of patients.Functional orthopedics are often used to correct the sagittal imbalance of mandible and mandible,and the large-scale displacement of condyle,which is one of the important reasons leading to TMJ osteoarthritis(TMJ OA).At present,the understanding of the pathogenesis and pathological essence of TMJ OA is not clear.In the past,the study of TMJ OA mainly focused on the mechanism of articular cartilage degeneration,while the study of subchondral bone was relatively rare.It has been confirmed that the activation of mTOR,especially mTORC1 signal in joints,is one of the important pathological factors in the progress of OA.Therefore,the purpose of this study is to investigate the expression of mTORC1 signaling pathway in cartilage and subchondral bone of condyle with functional orthopaedic overload,and to reveal the mechanism of TMJ OA induced by functional orthopaedic overload based on mTORC1 signaling pathway,so as to provide a new theory for its effective prevention and treatment.Methods:In this study,we mainly discussed the effect of mTORC1 signaling pathway on the course of OA.The expression of mTORC1 signaling pathway marker protein P-s6 in the subchondral bone of rat condylar process was observed at 2,4 and 8 weeks after the establishment of mandibular protrusion model.The joint degeneration and subchondral bone changes in rats were evaluated by histological and imaging methods.In addition,rapamycin was injected into the articular cavity of rats at the same time and histological methods were used.Imaging and Real-time PCR techniques were used to evaluate the joint degeneration and subchondral bone changes in rats after inhibition of mTORC1 signaling pathway in the subchondral bone of the condyle.Results:1.At 2、4 and 8 weeks after the establishment of the model,the condylar joint degeneration and TMJ OA appeared.HE staining indicated that the arrangement of chondrocyte was disordered and aggravated gradually with the prolongation of time.The arrangement of subchondral bone trabeculae was disordered and aggravated further with the prolongation of time.Safranine O-fixing green staining indicated that protein polysaccharide was lost in cartilage of EXP group at 2 weeks and became more serious with the prolongation of experimental time.At the same time,chondrocyte clustering and hypertrophy appeared.At 8 weeks, only a few positive areas remained in cartilage.2.The osteoblasts in the subchondral bone of mandibular protrusion rats showed significant activation of mTORC1 signal.3.Immunohistochemical results showed that osteogenesis and osteoclasts were significantly activated in the subchondral bone of the model rats,while osteoclasts were absorbed in the subchondral bone.4.Intra-articular injection of rapamycin inhibited the expression of mTORC1 in the subchondral bone of the condylar process in rats.5.Inhibiting the mTORC1 signaling pathway in the subchondral bone of the condyle of the rat model can inhibit the proliferation of osteoblasts,but has little effect on osteoclasts.6.Inhibiting the mTORC1 signaling pathway in the condyle of rats accelerates the bone resorption of subchondral bone.Conclusions:Activation of mTORC1,a key signaling pathway of subchondral osteoblasts,plays an important role in the regulation of joint degeneration in TMJ OA induced by mandibular protrusion overload.In view of the unclear understanding of the pathogenesis and pathological essence of TMJ OA,exploring the expression of mTORC1 signaling pathway in the condylar cartilage and subchondral bone with functional orthopedic overload provides a new theory for the effective prevention and treatment of TMJ OA.