Visfatin Increases VEGF-dependent Angiogenesis of Endothelial Progenitor Cells during Osteoarthritis Progression

• Main Authors: Chun-Hao Tsai, Shan-Chi Liu, Wen-Hui Chung, Shih-Wei Wang, Min-Huan Wu, Chih-Hsin Tang
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Cells
• Subjects: osteoarthritis; visfatin; VEGF; miR-485-5p; angiogenesis
• Online Access: https://www.mdpi.com/2073-4409/9/5/1315

Osteoarthritis (OA) pannus contains a network of neovascularization that is formed and maintained by angiogenesis, which is promoted by vascular endothelial growth factor (VEGF). Bone marrow-derived endothelial progenitor cells (EPCs) are involved in VEGF-induced vessel formation in OA. The adipokine visfatin stimulates the release of inflammatory cytokines during OA progression. In this study, we found significantly higher visfatin and VEGF serum concentrations in patients with OA compared with healthy controls. We describe how visfatin enhanced VEGF expression in human OA synovial fibroblasts (OASFs) and facilitated EPC migration and tube formation. Treatment of OASFs with PI3K and Akt inhibitors or siRNAs attenuated the effects of visfatin on VEGF synthesis and EPC angiogenesis. We also describe how miR-485-5p negatively regulated visfatin-induced promotion of VEGF expression and EPC angiogenesis. In our OA rat model, visfatin shRNA was capable of inhibiting visfatin and rescuing EPC angiogenesis and pathologic changes. We detail how visfatin affected VEGF expression and EPC angiogenesis in OASFs by inhibiting miR-485-5p synthesis through the PI3K and Akt signaling pathways.