Xiao-Yan Wang1, Yan Chen1, Xue-Jiao Tang1, Lin-Hong Jiang1, Ping Ji2. 1. Dental Student, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China. 2. Professor and Department Head, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China. Electronic address: jiping@sdu.edu.cn.
Abstract
PURPOSE: Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorder. This study investigated the inflammatory role of the stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor-4 (CXCR4) axis and the probable signaling pathway involved in matrix metalloprotease (MMP)-3 and MMP-9 productions stimulated by the SDF-1-CXCR4 axis in an experimental rat model of TMJOA. MATERIALS AND METHODS: Rats were randomly divided into a control group, a pathologic model group, and an AMD3100 group. Effects of the bicyclam derivative AMD3100 (the specific antagonist of SDF-1-CXCR4 axis) were studied in TMJOA experimentally induced by monosodium iodo-acetate. Productions of SDF-1 and CXCR4 were compared in the normal and pathologic model groups, and cartilage changes and expressions of MMP-3, MMP-9, and phosphorylated extracellular signal-regulated kinase (p-ERK) were compared in the control, pathologic model, and AMD3100 groups. RESULTS: Expressions of SDF-1 and CXCR4 in the pathologic model group were increased compared with the control group (P < .05). Releases of MMP-3, MMP-9, and p-ERK and cartilage changes were downregulated in the AMD3100 group compared with the pathologic model group (P < .05), and these changes occurred in a dose-dependent manner with AMD3100 concentrations. Moreover, there were strong predictive relations between the expression of p-ERK with MMP-3 (r(2) = 0.419; P < .001) and with MMP-9 (r(2) = 0.542; P < .001). CONCLUSIONS: The SDF-1-CXCR4 signaling pathway plays a proinflammatory role in experimental TMJOA, the bicyclam derivative AMD3100 can alleviate the severity of experimental TMJOA, and there might be a potential relation between the SDF-1-CXCR4 axis and the ERK signaling pathway.
PURPOSE:Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorder. This study investigated the inflammatory role of the stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor-4 (CXCR4) axis and the probable signaling pathway involved in matrix metalloprotease (MMP)-3 and MMP-9 productions stimulated by the SDF-1-CXCR4 axis in an experimental rat model of TMJOA. MATERIALS AND METHODS:Rats were randomly divided into a control group, a pathologic model group, and an AMD3100 group. Effects of the bicyclam derivative AMD3100 (the specific antagonist of SDF-1-CXCR4 axis) were studied in TMJOA experimentally induced by monosodium iodo-acetate. Productions of SDF-1 and CXCR4 were compared in the normal and pathologic model groups, and cartilage changes and expressions of MMP-3, MMP-9, and phosphorylated extracellular signal-regulated kinase (p-ERK) were compared in the control, pathologic model, and AMD3100 groups. RESULTS: Expressions of SDF-1 and CXCR4 in the pathologic model group were increased compared with the control group (P < .05). Releases of MMP-3, MMP-9, and p-ERK and cartilage changes were downregulated in the AMD3100 group compared with the pathologic model group (P < .05), and these changes occurred in a dose-dependent manner with AMD3100 concentrations. Moreover, there were strong predictive relations between the expression of p-ERK with MMP-3 (r(2) = 0.419; P < .001) and with MMP-9 (r(2) = 0.542; P < .001). CONCLUSIONS: The SDF-1-CXCR4 signaling pathway plays a proinflammatory role in experimental TMJOA, the bicyclam derivative AMD3100 can alleviate the severity of experimental TMJOA, and there might be a potential relation between the SDF-1-CXCR4 axis and the ERK signaling pathway.
Authors: Lei Ding; Cheng Zhou; Hongjun Zheng; Quanming Wang; Haiyan Song; Joseph A Buckwalter; James A Martin Journal: Cartilage Date: 2021-10-12 Impact factor: 3.117