Nowadays, the biological activity of collagen peptides has been revealed, but the effect of Atlantic salmon (Salmo salar) bone-derived collagen peptide (CPs) on osteoarthritis remains unclear. In this study, CPs was identified as a small molecular weight peptide rich in Gly-X-Y structure. Meanwhile, interleukin-1β (IL-1β)-induced hypertrophic chondrocytes and partial medial meniscectomy (pMMx) surgery model in rats were performed. In IL-1β stimulated chondrocytes, CPs significantly increased the type-II collagen content, reduced the type-X collagen abundance and chondrocytes apoptosis. Meanwhile, CPs reversed the increased expression of matrix metalloproteinase, metalloproteinase with thrombospondin motifs and RUNX family transcription factor 2 in chondrocytes induced by IL-1β. In vivo, CPs increased pain tolerance of rats and without organ toxicity at 1.6 g/kg.bw. CPs significantly decreased the levels of COMP and Helix-II in serum. Furthermore, a significant decrease of IL-1β in synovial fluid and cartilage tissue were observed by CPs intervention. From Micro-CT, CPs (0.8 g/kg.bw) significantly decreased Tb.sp and SMI value. Meanwhile, the expression of tumor necrosis factor and interleukin-6 were reduced by CPs administration both in vitro and in vivo. Together, CPs showed potential to be a novel and safe dietary supplement for helping anti-inflammatory and cartilage regeneration, ultimately hindering osteoarthritis development. However, the clear mechanism of CPs's positive effect on osteoarthritis needs to be further explored.
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