Bletilla striata polysaccharide inhibits osteoclast differentiation by suppressing macrophage glycolysis and MMP9 expression.

Utilizing single-cell RNA sequencing and network pharmacology, this study explored the mechanism by which Bletilla striata polysaccharide (BSP) mitigates peri-implantitis-associated osteolysis. Integrated analyses revealed a significant expansion of pro-inflammatory macrophages and osteoclasts in diseased tissues, with differentially expressed genes enriched in glycolytic pathways. Mechanistic exploration indicated that BSP suppresses osteoclastogenesis primarily by targeting matrix metalloproteinase-9 (MMP9), thereby inhibiting proteolytic activity and cytoskeletal remodeling. Preliminary rescue experiments supported this notion, showing that while BSP effectively downregulated LPS-induced MMP9 upregulation and suppressed macrophage glycolytic metabolism, forced overexpression of MMP9 partially restored MMP9 levels and reversed the inhibitory effect of BSP on osteoclast formation. These findings suggest a potential "metabolism-protease" interplay, where BSP concurrently modulates immune metabolism and protease activity to alleviate inflammatory bone loss, providing a foundational basis for developing plant-derived polysaccharide therapeutics.