The effect of Fasudil on degradation of chondrocyte matrix and its mechanism
JI Encheng1, Zhou Yeli1, Chen Chengwei1, Chen Chun1, Li Jing1, Gao Weiyang2, Pan Zhe’er1
1.Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Hand Surgery, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
JI Encheng,Zhou Yeli,Chen Chengwei, et al. The effect of Fasudil on degradation of chondrocyte matrix and its mechanism[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(8): 557-562.
Abstract：Objective: To study the effect of Fasudil on matrix degradation of humolan chondrocytes and to explore its possible mechanism. Methods: CCK-8 was used to determine whether Fasudil was toxic and to determine the appropriate drug concentration. The cells were grouped as control group, Fasudil group, IL-1β group and Fasudil+IL-1β group. NO levels were determined by nitrate reductase assay; Western blot was used to detect COX-2, iNOS, MMP-13, p-MYPT, ROCK1, ROCK2, p-Erk/Erk, p-JNK/JNK and p-p38/p38 levels; qRT-MMP-13 and collagen-II expressions were determined by PCR; cell immunofluorescence was used to detect the expressions of MMP-13. Results: Compared with the IL-1β group, ROCK1, ROCK2 and p-MYPT were inhibited in the Fasudil+IL-1β group; the expression of COX-2, NO, iNOS and MMP-13 was inhibited, so did the expression of p-Erk, p-JNK and p-p38; the phosphorylation levels of Erk, JNK and p38 were decreased, and the expression of collagen-II was up-regulated. The differences were statistically significant (P<0.05). Conclusion: Fasudil inhibited IL-1β-induced degradation of chondrocyte matrix, which is probably achieved by inhibiting MAPK signaling pathway.
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