Chondrocyte apoptosis in rat mandibular condyles induced by dental occlusion due to mitochondrial damage caused by nitric oxide. (May 2019)

• Record Type: Journal Article
• Authors: Ren, Haotian; Yang, Hongxu; Xie, Mianjiao; Wen, Yi; Liu, Qian; Li, Xiaomei; Liu, Jun; Xu, Haokun; Tang, Weizhong; Wang, Meiqing
• Is Part Of: Archives of oral biology. Volume 101(2019)
• Page Start: 108
• Page End: 121
• Publication Date: 2019-05
• Subjects: NO nitric oxide -- iNOS inducible nitric oxide synthase -- nNOS neuronal nitric oxide synthase -- eNOS endothelial nitric oxide synthase -- L-NAME NΩ-nitro-l-arginine methyl ester hydrochloride -- TUNEL terminal-deoxynucleotidyl transferase-mediated nick end labeling -- JC-1 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl benzimidazole carbocyanine -- SOD superoxide dismutase -- Cyt C cytochrome C -- Bcl-2 B cell lymphoma-2 -- Bax Bcl-2-associated X protein -- PARP1 poly-ADP-ribose polymerase 1 -- APAF-1 apoptotic protease activating factor-1 -- MMP matrix metalloproteinase -- Col2 type II collagen -- HE hematoxylin-eosin -- SO safranin O staining -- IHC immunohistochemical staining -- PCR polymerase chain reaction -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- GAPDH glyceraldehyde-phosphate dehydrogenase -- Adamts5 A disintegrin and metalloproteinase with thrombospondin motifs 5 -- ANOVA one-way analysis of variance -- SD standard deviation; Apoptosis -- Cartilage -- Dental occlusion -- Nitric oxide -- Biomechanics; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2019.03.006
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: Two kinds of abnormal biomechanical stimulation models were used both in vivo and in vitro. Temporomandibular joint osteoarthritis is related to mitochondrial injury. Mitochondrial injury can be caused by an increase in nitric oxide. Targeting mitochondrial pathway can be a strategy for the treatment of osteoarthritis. Abstract: Objective: Chondrocyte apoptosis is a pathological manifestation of osteoarthritis. The goal of this report was to explore the role of nitric oxide in chondrocyte apoptosis in osteoarthritic mandibular condylar cartilage. Design: This study used our reported experimental unilateral anterior crossbite in vivo rat model and chondrocyte fluid flow shear stress in vitro model. In the in vivo model, apoptosis in the mandibular condylar cartilage was assessed by detection of the TUNEL-positive cells, the expression levels of inducible nitric oxide synthase (iNOS), caspase-9, and caspase-3. In the in vitro model, mitochondrial injury was evaluated, the nitric oxide and superoxide dismutase (SOD) production levels were measured, and the cytochrome C (Cyt C) expression level was detected. The expression levels of apoptosis-related proteins B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, and poly-ADP-ribose polymerase 1 (PARP1) were analyzed in both in vivo and in vitro models. The effects of iNOS inhibitor on chondrocyte apoptosis were also investigated. Results: The data indicated that the unilateral anterior crossbite induced cartilage degeneration with enhanced cell apoptosis and stimulated the expression of caspase-3/-9 and iNOS. The fluid flow shear stress upregulated the expression of iNOS, SOD, and nitric oxide, reduced mitochondrial membrane potential, and promoted Cyt C to enter the cytoplasm. All of these changes were reversed by iNOS inhibitors. Conclusion: The abnormal occlusion stimulated mitochondrial damage and apoptosis of the chondrocytes in the mandibular condylar cartilage mediated by nitric oxide. Inhibiting nitric oxide production could be a therapeutic strategy.