Role of BLACAT1 in IL-1 beta-Induced Human Articular Chondrocyte Apoptosis and Extracellular Matrix Degradation via the miR-149-5p/HMGCR Axis

Background: Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development. Objectives: In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA. Methods: Interleukin (IL)-1 beta was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1 beta-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing. Results: In IL-1 beta-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR-149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation. Conclusion: LncRNA BLACAT1 was overexpressed in IL-1 beta-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.