Molecular Docking and Functional Analyses Reveal the Chondroprotective and Anti-Inflammatory Potential of Statins in Osteoarthritis.

Osteoarthritis is a progressive degenerative joint disorder characterised by cartilage degradation and chronic inflammation. Beyond their well-established lipid-lowering properties, statins, particularly pitavastatin and rosuvastatin, have demonstrated promising anti-inflammatory and chondroprotective effects. This study comprehensively evaluated these effects on human primary chondrocytes using an integrative approach involving in silico and in vitro experiments. Key molecular targets, including NF-κB, IL-1β and SOX9, were analysed to elucidate the mechanisms underlying the therapeutic potential of these statins. Molecular docking analyses using the CB-Dock2 platform revealed strong binding affinities of both statins with the target proteins, with pitavastatin exhibiting a higher binding score (-8.0) compared to rosuvastatin (-7.9). Bioinformatics analyses via STITCH and STRING databases highlighted the involvement of both statins in pathways regulating inflammation, lipid metabolism, and cartilage homeostasis. In vitro experiments demonstrated that both statins preserved chondrocyte viability at 24 and 48 h; however, prolonged exposure led to significant declines, with rosuvastatin exhibiting greater cytotoxicity. Western blot analyses confirmed that both statins effectively suppressed IL-1β expression, indicative of potent anti-inflammatory activity. Pitavastatin transiently enhanced SOX9 expression, peaking at 24 h before declining, while rosuvastatin showed a more sustained but moderate increase. NF-κB expression steadily increased over time with both statins, suggesting potential activation of compensatory inflammatory pathways during prolonged exposure. These findings underscore the dual anti-inflammatory and chondroprotective roles of pitavastatin and rosuvastatin, while highlighting the need for careful consideration of dosage and treatment duration to mitigate cytotoxic effects and provide novel insights into the molecular mechanisms of statins.