TY - JOUR TI - Cartilage tissue miR-214-3p regulates the TrkB/ShcB pathway paracrine VEGF to promote endothelial cell migration and angiogenesis AU - Xiao, Peng AU - Zhu, Xu AU - Sun, Jinpeng AU - Zhang, Yuhang AU - Qiu, Weijian AU - Li, Jianqiang AU - Wu, Xuejian T2 - Bone AB - Background This study was designed to explore the mechanisms through which chondrocytes regulated endothelial cell migration and angiogenesis in Osteoarthritis (OA). Methods The expressions of related genes of OA were detected by Western blot and real-time quantitative PCR. Chondrocytes were co-cultured with endothelial cells, and migration as well as angiogenesis rates, and vascular endothelial growth factor (VEGF) secretion of the cells were detected. The relationship between miRNA and TrkB were analyzed by bioinformatics analysis, RNA immunoprecipitation and dual-luciferase assays. The effects of miRNA on the histopathology of the OA mice were determined. Results The expressions of NGF, TrkA, TrkB, and ShcB were increased significantly in OA patients. IL-1β promoted the expressions of TrkA, TrkB, and ShcB in chondrocytes and inhibited the expressions of chondrogenic differentiation markers, but shTrkB partially reversed IL-1β-mediated chondrogenic differentiation. Overexpression of TrkB promoted cell migration, angiogenesis, and VEGF levels, while silencing ShcB reversed the regulation of TrkB. Moreover, chondrocytes miR-214-3p regulated endothelial cell migration and angiogenesis by targeting TrkB paracrine VEGF to activate PI3K/Akt pathway proteins. In addition, overexpressed miR-214-3p improved collagenase-induced cartilage and synovial damage in OA mice. Conclusion The activation of TrkB/ShcB signaling pathway paracrine VEGF is mediated by miR-214-3p in chondrocytes and it regulates endothelial cell migration and angiogenesis in the development of OA. DA - 2021/06/06/ PY - 2021 DO - 10.1016/j.bone.2021.116034 DP - ScienceDirect SP - 116034 J2 - Bone LA - en SN - 8756-3282 UR - https://www.sciencedirect.com/science/article/pii/S8756328221001964 Y2 - 2021/06/10/21:53:16 KW - Chondrocytes KW - Endothelial cells KW - Osteoarthritis KW - TrkB/ShcB KW - miR-214-3p ER -