Lactobacillus sakei CVL-001 Inhibits Osteoclast Differentiation Through TLR2 and GPCR-Dependent Pathways and Prevents Bone Loss in Ovariectomized Mice.

Postmenopausal osteoporosis is a common bone disease characterized by bone loss due to the disruption of bone homeostasis caused by decreased estrogen levels. It is estimated that approximately one third of women over the age of 50 will experience osteoporosis in their lifetime. Therefore, developing functional foods or treatments that can be safely consumed to prevent bone disease is essential. Recent studies have reported that gut microbiota is closely related to the development of osteoporosis. In this study, we confirmed that Lactobacillus sakei CVL-001 (CVL-001) and its metabolites (CVL-001S) alleviate OVX-induced bone loss. Furthermore, they inhibited RANKL-induced osteoclastogenesis by regulating NFATc1 expression. Imbalance in the gut microbiota also affects the release of cellular components such as lipoteichoic acid and exopolysaccharides from beneficial bacteria (e.g., lactic acid bacteria), as well as production metabolites such as short chain fatty acid. Therefore, to investigate the association between CVL-001S-mediated inhibition of osteoclast differentiation, we used osteoclast precursor cells isolated from TLR2 KO mice and the GPCR inhibitor. Although the inhibitory effect of CVL-001S on osteoclast differentiation could not be fully rescued by either the TLR2 KO cells or the GPCR inhibitor alone, pretreatment of TLR2 KO cells with the GPCR inhibitor completely abolished the inhibitory effect of CVL-001S on osteoclast differentiation. These results suggest that CVL-001S inhibits RANKL-induced osteoclast differentiation through the cooperation of TLR2 with GPCR. Our results suggest that CVL-001S and CVL-001 can be a potentially therapeutic agent for preventing or treating bone disease.