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

Chun-Hao Tsai,Min-Huan Wu,Shih-Wei Wang,Wen-Hui Chung,Chih-Hsin Tang,Shan-Chi Liu

doi:10.3390/cells9051315

Abstract

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.

Highlights

Osteoarthritis (OA) is a common age-related and chronic degenerative joint disorder that affects all body joints
In our initial exploration of visfatin and vascular endothelial growth factor (VEGF) expression in OA development, ELISA test results revealed significantly higher visfatin and VEGF serum concentrations in patients with OA compared with healthy controls (Figure 1A,B and Supplementary Material Tables S1 and S2)
We found that visfatin stimulates endothelial progenitor cells (EPCs) angiogenesis in OA synovial fibroblasts (OASFs) by increasing VEGF

Summary

Introduction

Osteoarthritis (OA) is a common age-related and chronic degenerative joint disorder that affects all body joints. Major symptoms of OA include cartilage degradation, osteophyte formation, bone remodeling, neoangiogenesis, and synovial inflammation [1], which are associated with pain, physical disability, and substantial impairments in quality of life. The synovium plays an important role in the pathogenesis of OA. The synthesis of chondrolytic enzymes and proinflammatory mediators by the. Cells 2020, 9, 1315 inflamed synovium leads to cartilage destruction, which in turn enhances synovial inflammation [2,3]. OA synovial fibroblasts (OASFs) sustain arthritic pathology by excreting chondrolytic enzymes and inflammatory mediators [2,4,5]. Synovium-targeted therapy could slow OA progression and mitigate the disease symptoms [6,7]

Methods

Results

Conclusion