Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan.
Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan.
J Bone Miner Res. 2022 Oct;37(10):1944-1955. doi: 10.1002/jbmr.4661. Epub 2022 Aug 8.
Osteoarthritis (OA) is associated with extensive upregulation of osteoclastogenesis and subsequent bone breakdown. The CCN family protein connective tissue growth factor (CCN2, also called CCN2) enhances inflammatory cytokine production in OA disease. The cytokine interleukin (IL)-17 is known to induce osteoclastogenesis and bone erosion in arthritic disease. Our retrieval of data from the Gene Expression Omnibus (GEO) data set and clinical tissues exhibited higher CCN2 and IL-17 expression in OA synovial sample than in normal healthy samples. We observed the same phenomenon in synovial tissue from rats with anterior cruciate ligament transaction (ACLT)-elicited OA compared with synovial tissue from control healthy rats. We also found that CCN2 facilitated increases in IL-17 synthesis in human OA synovial fibroblasts (OASFs) and promoted osteoclast formation. CCN2 affected IL-17 production by reducing miR-655 expression through the ILK and Syk signaling cascades. Our findings improve our understanding about the effect of CCN2 in OA pathogenesis and, in particular, IL-17 production and osteoclastogenesis, which may help with the design of more effective OA treatments. © 2022 American Society for Bone and Mineral Research (ASBMR).
骨关节炎（OA）与破骨细胞生成的广泛上调以及随后的骨破坏有关。细胞外基质蛋白连接蛋白（CCN）家族蛋白结缔组织生长因子（CCN2，也称为 CCN2）增强 OA 疾病中的炎性细胞因子产生。细胞因子白细胞介素（IL）-17 已知可诱导关节炎疾病中的破骨细胞生成和骨侵蚀。我们从基因表达综合数据库（GEO）数据集和临床组织中检索的数据显示，OA 滑膜样本中的 CCN2 和 IL-17 表达高于正常健康样本。我们在 ACLT 诱发的 OA 大鼠的滑膜组织中观察到了与对照健康大鼠相同的现象。我们还发现 CCN2 通过减少 ILK 和 Syk 信号级联反应中的 miR-655 表达促进人 OA 滑膜成纤维细胞（OASF）中 IL-17 的合成，并促进破骨细胞形成。CCN2 通过减少 ILK 和 Syk 信号级联反应中的 miR-655 表达，影响 IL-17 的产生。我们的发现增进了对 CCN2 在 OA 发病机制中的作用的理解，特别是对 IL-17 产生和破骨细胞生成的理解，这可能有助于设计更有效的 OA 治疗方法。© 2022 美国骨骼矿物质研究协会（ASBMR）。
