BCL6 Promotes Transcription of GPR61 to Suppress IL-1β-Induced Osteoarthritis Progression in C28/I2 Cells

Osteoarthritis (OA) is the most common joint disease and its pathogenic mechanism remains to be ensured. This study focused on the regulatory relation between B-cell lymphoma 6 (BCL6) and G-protein-coupled receptor 61 (GPR61) underlying IL-1β in OA. Real-time quantitative polymerase chain reaction and western blot were performed for mRNA and protein detection. Oxidative injury was assessed by reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) via kits. Fe level was measured via an iron assay kit. Relation analysis between BCL6 and GPR61 was implemented employing ChIP assay and dual-luciferase reporter assay. GPR61 was downregulated in OA samples and IL-1β-induced C28/I2 cells. IL-1β-induced cell inflammation, extracellular matrix (ECM) degradation, oxidative stress, and ferroptosis were all returned by overexpression of GPR61. BCL6 downregulation was detected in OA patients and IL-1β-exposed C28/I2 cells. BCL6 could promote the transcription of GPR61. BCL6 suppressed IL-1β-induced OA progression by upregulating GPR61. The BCL6/GPR61 axis activated the PKA/CREB pathway in IL-1β-treated C28/I2 cells. The above results suggested that BCL6 mitigated OA progression induced by IL-1β by enhancing transcription of GPR61. BCL6/GPR61/PKA/CREB axis may be considered as a novel regulatory mechanism in OA, and BCL6 has the potential to act as a novel target for OA.