Crucial role of low molecular weight chondroitin sulfate from hybrid sturgeon cartilage in osteoarthritis improvement: Focusing on apoptosis, systemic inflammation, and intestinal flora

Low molecular weight chondroitin sulfate (CS) has gained considerable attention for its superior bioactivity compared to native CS. In this study, the mechanisms of low molecular weight chondroitin sulfate from hybrid sturgeon cartilage (LMSCS), prepared using the H₂O₂/Vc system, on the remission of osteoarthritis (OA) were investigated both in in vitro and in vivo. A Caco-2/SW1353 co-culture cell model and a monosodium iodoacetate (MIA)-induced OA mouse model were used to validate its inhibited apoptosis, anti-inflammatory effects, and intestinal flora modulation. LMSCS was found to effectively alleviate inflammation, decrease chondrocyte apoptosis, and reduce MMP-13 levels by inhibiting the activation of NF-κB and MAPK signaling pathways. Notably, in vivo experiments, LMSCS exhibited significant anti-inflammatory effects compared to SCS. This trend, however, was not observed in vitro, which could be largely attributed to LMSCS' ability to regulate intestinal flora. Compared to SCS, LMSCS enhanced the abundance of beneficial bacteria, particularly, the Prevotellaceae_NK3B31_group and Akkermansia, and increased the levels of short-chain fatty acids such as butyrate and propionate. The effectiveness of LMSCS in mitigating inflammatory responses in vivo is thus largely due to its intestinal flora modulation, providing for its development and application.