CircHYBID Regulates Hyaluronan Metabolism in Chondrocytes by Promoting the Expression of the hsa-miR-29b-3p Target Gene TGF-β1

Background: Hyaluronan (HA) metabolism by chondrocytes is essential for cartilage development and homeostasis. However, the function of circular RNAs (circRNAs)in HA metabolism is limited. In this study, we profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis.Methods: The function of circHYBID in HA metabolism in chondrocytes was investigated using gain-of-function experiments. The mechanism of HA-binding protein involved in hyaluronan depolymerization (HYBID) was confirmed through bioinformatics analysis and luciferase assays. The expression correlation of the circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by qRT-PCR and western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using immunohistochemistry. ELISA assay was used to assess HA accumulation in chondrocyte supernatant.Results: CircHYBID expression was significantly downregulated in damaged cartilage samples comparing with that in the corresponding intact cartilage samples. CircHYBID expression was inversely correlated with the Mankin score and positively correlated with HA expression. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis illustrated that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions: Our results describe a novel HA-related circRNA that could promote the synthesis and accumulation of HA. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and Osteoarthritis (OA) progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.