Chondroprotective Effects of Enzyme-Treated Extract from Cervus elaphus L. in a Rat Model of Osteoarthritis

Osteoarthritis (OA) is a chronic, debilitating degenerative joint disease whose prevalence is rising markedly with the rapid aging of the global population. In this study, we investigated the chondroprotective efficacy of NP-2007, an enzymatically hydrolyzed low-molecular-weight collagen from Cervi cornu, using IL-1β-stimulated SW1353 human chondrocyte cells and a medial meniscal transection (MMT)-induced OA rat model. In SW1353 cells, NP-2007 considerably suppressed the expression of inflammatory mediators (iNOS, COX-2) and cytokines (TNF-α, IL-6) without cytotoxicity. Crucially, it restored matrix homeostasis by downregulating catabolic enzymes (MMP-3, MMP-13, and ADAMTS-5) and upregulating anabolic markers (COL2A1, aggrecan), a process associated with the modulation of the Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways and the recovery of the master chondrogenic factor SOX9. These in vitro findings were consistent with the in vivo results from the MMT model, where oral administration of NP-2007 (50 and 200 mg/kg) for 8 weeks effectively preserved articular cartilage structure and proteoglycan content while markedly reducing serum levels of catabolic biomarkers, including MMP-13 and COMP. Collectively, our findings demonstrate that NP-2007 exerts potent chondroprotective effects by modulating the balance between cartilage degradation and synthesis, suggesting its potential as a therapeutic candidate for the management of OA.