Chinese herbal compound Xinfeng capsule inhibits cartilage extracellular matrix degradation and inflammation in osteoarthritis by modulating circ_0032131 and the miR-502-5p/TRAF2 axis

Abstract

Objective We intended to explore the anti-inflammatory and chondroprotective effects of Xinfeng capsule (XFC) in osteoarthritis (OA), perhaps through the regulation of hsa_circ_0032131 and miR-502-5p/TRAF2 axis. Materials and methods In total, 30 patients with OA and healthy subjects were recruited. To detect markers of cartilage metabolism and inflammation, peripheral blood mononuclear cells (PBMCs) were taken out. Subsequently, network pharmacology was employed to forecast OA-related targets and pathways for XFC therapy. To investigate the function of upregulated hsa_circ_0032131 in model cells.A series of functional experiments revealed the relationship between hsa_circ_0032131 and miR-502-5p/TRAF2 axis. To further determine whether XFC potentially treats OA through the interaction between circ_0032131 and miR-502-5p/TRAF2 axis. CKK-8 assay and flow cytometry were performed to detect cell proliferation and apoptotic processes in XFC-treated cells. Some conventional experimental methods were used to detect the expression levels of inflammatory factors, extracellular matrix and others. In addition, rescue experiments verified that XFC blocked the effects of hsa_circ_0032131 overexpression on extracellular matrix, inflammation and cell viability. Results Clinical observations indicated that the expression of hsa_circ_0032131 in PBMCs of OA patients was significantly elevated, and there was a correlation with clinical immuno-inflammatory factors and inflammatory indicators. Network pharmacology verified that the chief active ingredients of XFC exerted their roles mainly in the regulation of inflammation (IL1A, IL1B, IL4), extracellular matrix metabolism (MMP13, COL2A1), and tumour necrosis factor (TNF, TRAF2). In vitro experiments revealed that knockdown of circ_0032131 inhibited apoptosis, inflammatory and ECM degradation in PBMCs-stimulated chondrocytes. Circ_0032131 was verified to be a sponge of miR-502-5p by targeting, and TRAF2 was a direct target of miR-502-5p. By regulating circ_0032131 and miR-502-5p/TRAF2 axis, XFC prevented PBMCs-stimulated chondrocytes from responding to inflammation and ECM degradation. Conclusion The XFC suppressed inflammatory response and extracellular matrix metabolism in OA by regulating circ_0032131 and miR-502-5p/TRAF2 axis.