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

Abstract

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. 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. 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 (<i>p</i> < 0.05). However, it significantly reduced the expression of critical proteins including HIF-1α, SOX9, and IL-1β (<i>p</i> < 0.05). 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. The online version contains supplementary material available at 10.1186/s13018-025-06068-5.