Venom-Derived Proteins from Lonomia obliqua Modulate Cytoskeletal Regulators and Inflammatory Responses in Human Chondrocytes

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, extracellular matrix degradation, chondrocyte apoptosis, and elevated inflammatory mediators. Chondrocytes respond to IL-1β and other inflammatory signals by secreting cytokines and activating transcriptional pathways that perpetuate inflammation. Because current therapies do not prevent OA progression, bioactive compounds with cytoprotective and immunomodulatory activity are of considerable interest. Lonomia obliqua bristle extract (LOCBE) and its recombinant proteins rLOPAP and rLOSAC exhibit cytoprotective, proliferative, and antioxidant effects in mammalian cells, as well as the ability to influence cytoskeletal dynamics. Given the importance of Rac-1, RhoA, Rab9, and β-catenin in chondrocyte function and cartilage homeostasis, we evaluated LOCBE, rLOPAP, and rLOSAC in human chondrocytes stimulated or not with IL-1β. LOCBE and rLOPAP induced IL-6 and IL-8 secretion, although at lower levels than IL-1β. LOCBE exerts a cytoprotective effect in IL-1β-treated chondrocytes and reduces β-catenin, RhoA, and Rab9 expression without affecting NF-κB p65 translocation. rLOPAP increased mitochondrial activity, cytokine secretion, Rab9 expression, and membrane-associated β-catenin, and under inflammatory conditions, enhanced Rac-1 levels. In contrast, rLOSAC did not induce inflammatory cytokines and decreased RhoA and Rac-1 expression while increasing membrane-associated β-catenin. These findings suggest that L. obliqua extract and its derived-proteins rLOPAP and rLOSAC modulate cytoskeletal regulatory pathways and inflammatory responses in chondrocytes, supporting their potential as therapeutic leads for targeting mechanisms relevant to OA progression.