Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway.

BACKGROUND: This study aimed to investigate the effects of Lopinavir/Ritonavir (Lop/r) on chondrocyte structure and extracellular matrix (ECM) integrity, as well as its impact on key proteins involved in anabolic and catabolic pathways, using both in vitro and in silico approaches. METHODS: Drug-target interaction networks were constructed through bioinformatics analyses, and molecular docking was performed. Human primary chondrocytes were treated with Lop/r, and untreated cells served as controls. Cell viability, proliferation, and protein expression levels were assessed using standard in vitro techniques, including spectrophotometric assays and Western blotting. RESULTS: Molecular docking analyses revealed strong binding affinities between Lop/r and osteoarthritis-related targets such as HIF-1α, EP300, TNF, IL-6, KCNA5, and IL-1β, suggesting modulation of hypoxia, inflammatory, and epigenetic pathways. In vitro, Lop/r did not alter chondrocyte morphology or ECM structure and was not cytotoxic (p < 0.05). However, it significantly reduced the expression of critical proteins including HIF-1α, SOX9, and IL-1β (p < 0.05). CONCLUSION: These findings suggest that Lop/r may exert regulatory effects on cartilage-related molecular pathways and holds promise as a repurposed therapeutic agent for osteoarthritis. Further studies are warranted to confirm its potential in clinical applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-025-06068-5.