Xueting Luo1, Yangmei Jiang1, Ruiye Bi1, Nan Jiang1, Songsong Zhu2. 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. 2. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: 59654046@qq.com.
Abstract
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.
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.
Authors: Christopher Phillip Chen; Jiehua Zhang; Bin Zhang; Mohamed G Hassan; Kyle Hane; Caroline C Chen; Ana Alejandra Navarro Palacios; Sunil Kapila; Andrew H Jheon; Alice F Goodwin Journal: JBMR Plus Date: 2022-07-03