Anti-osteoporosis activity and mechanism analyses of Limosilactobacillus fermentum YSC5001 from Chinese traditional dairy products

Osteoporosis is prevalent, poses significant health risks, and is often overlooked in public health. Lactic acid bacteria (LAB) have emerged as a promising alternative for osteoporosis prevention, especially given the adverse effects of conventional treatments. In this study, Limosilactobacillus fermentum YSC5001 was identified as the most effective strain among 64 edible LAB isolates for enhancing pre-osteoblastic MC3T3-E1 cell differentiation and mineralization. Using a tail-suspended rat model, YSC5001 increased bone mineral density by 63.10 % and reduced osteoclastogenesis by 54.65 %. It also improved biomechanical properties and lowered inflammatory markers, with IL-1β and TNF-α levels decreasing by 21.41 % and 30.08 %, respectively. Further analysis suggested that YSC5001 modulates the Wnt/β-catenin pathway via secretion of 2-hydroxy-3-methylbutyric acid, arginine, and lysine, thereby alleviating osteoporosis. Notably, YSC5001 is a food-derived strain with demonstrated safety and no detectable virulence or antibiotic resistance genes, supporting its application as an oral probiotic for osteoporosis management. • Limosilactobacillus fermentum YSC5001 enhances osteoblast differentiation and mineralization. • YSC5001 improves bone microstructure and biomechanical properties in osteoporotic rats. • The strain regulates bone metabolism by modulating key bone formation and resorption markers. • 2-Hydroxy-3-methylbutyric acid, arginine, and lysine activate Wnt10b/β-catenin signaling to promote osteogenesis.