Abstract
Background:Our team have previously reported that Adiponectin correlates well with synovial inflammation and progressive bone erosion in rheumatoid arthritis (RA). Angiogenesis is another important part, which plays a critical role in the pathogenesis of RA.Objectives:We hypothesized that adiponectin induces synovial angiogenesis in RA.Methods:Single-cell RNA sequencing (scRNA-Seq) was used to screen cellular changes in local knee joint of collagen-induced arthritis (CIA) after intraarticularly injected of adiponectin. Chimera models of synovium-cartilage-NOD/SCID mice, matrigel plug assay and rat aortic ring assay were performed to demonstrate the pro-angiogenesis role of adiponectin. Cellular experiment, including proliferation, migration, apoptosis, tube formation and angiogenesis related gene expression profile, were detected with Human Umbilical Vein Endothelial Cells (HUVEC) and Mice Lung Microvessel Endothelial Cell (MLMEC) after adiponectin stimulation. Seahorse was performed to clear the influence of adiponectin to cell metabolism.Results:The synovium and pannus hyperplasia worse in CIA model after intraarticularly injected of adiponectin, along with more serious synovitis and bone erosion. ScRNA-Seq of synovial tissues separated from CIA reminded that endothelial cell barbarically grows via metabolic remodeling after stimulated with adiponectin. Synovial chimera, matrigel plug and rat aortic ring shows adiponectin accelerates angiogenesis significantly in different background conditions. In vitro, endothelial cell proliferation detecting by RCTA and CCK8, migration by wound healing and transwell, apoptosis by FACS, tube formation and angiogenesis related gene expression profile by PCR-ARRAY were promoted by adiponectin in both HUVEC and MLMEC. Seahorse showed HUVEC made more use of glycolysis after co-cultured with adiponectin, a method of cell energy supply that tumor cells possess called warburg effect, that drives endothelial cell hyperplasia in severe environment.Conclusion:As a classic metabolic regulator, adiponectin exacerbates CIA by promoting angiogenesis through metabolic remodeling. The findings not only provide a novel insight into the pathogenic role of adiponectin, but also reveals a potential therapeutical strategy to attenuate revascularization in RA.Disclosure of Interests:None declared
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