Inhibition of notch signaling pathway temporally postpones the cartilage degradation progress of temporomandibular joint arthritis in mice

Purpose: The aim of this study is to explore the role of Notch signaling pathway in the initiation and progression of temporomandibular joint osteoarthritis (TMJOA). Methods: 48 mice were divided into DAPT-TMJOA, Control-TMJOA and Control-Sham groups. Animals received discectomy/Sham surgery in their right TMJ, following the DAPT/saline intra-articular injections every week. Mice were sacrificed at 1/4/8 weeks post-surgery. Safranin-O and H&E staining were performed on the TMJ sections for the modified Mankin's score. qPCR and immunohistochemistry were used to evaluate Notch1, Jagged1 and Hes5 expressions. Results: The mRNA expressions of Notch1, Jagged1 and Hes5 were significantly increased in Control-TMJOA group compared with Control-Sham group. Immunostaining revealed a dramatic elevation of Notch1, Jagged1 and Hes5 signals distributed in the cartilage at 1 and 4 weeks after discectomy. However, the increased number of those immuno-positive cells turned down at 8 weeks after surgery. DAPT treatment partially rescued the elevated mRNA expression and immuno-positive cell numbers of Notch1, Jagged1 and Hes5. More importantly, the cartilage destruction during TMJOA was delayed by DAPT treatment, analyzed by modified Mankin's score. Conclusion: Notch signaling participates in the onset and development of TMJOA. Inhibiting Notch signaling activation by DAPT can partially delay the progress of TMJOA. (C) 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.