Comparative Evaluation of Bovine and Porcine-Derived Chondroitin Sulfate on Osteoarthritis Amelioration: A Metabolomics-Based Study

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration. Chondroitin sulfate (CS), a natural glycosaminoglycan, has been reported to be effective in alleviating OA symptoms, but its efficacy can vary depending on the raw material. This study compared the therapeutic effects of bovine-derived CS and porcine-derived CS on OA, focusing particularly on cartilage markers and metabolic changes. In vitro experiments showed that both types of CS reduced the expression of the cartilage-degrading enzyme MMP-13 in H²O²-stimulated MG-63 cells. In vivo experiments showed that the oral administration of CS (123.3 mg/kg) to monosodium iodoacetate-induced arthritic rats for four weeks increased the expression of the cartilage anabolic markers ACAN and COL2A1 while decreasing the catabolic marker MMP-13. Serum metabolite analysis showed that CS supplementation modulated the metabolites associated with inflammation, oxidative stress, and cartilage metabolism, with porcine-derived CS exhibiting a more pronounced effect than bovine-derived CS in terms of the metabolic profile and restoration of cartilage integrity. Furthermore, high-performance liquid chromatography showed that porcine-derived CS contains a higher proportion of C4S compared to bovine-derived CS, and this difference in 4S/6S disaccharide composition appears to contribute to the distinct chondroprotective and metabolic recovery effects observed between the two sources. These findings suggest that oral CS supplementation may mitigate OA progression by restoring cartilage homeostasis and regulating the systemic metabolism, with porcine-derived CS showing superior efficacy.