3′-Sialyllactose alleviates bone loss by regulating bone homeostasis

Abstract

Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3 '-Sialyllactose (3 '-SL) in human milk regulates many biological functions. However, its effect on bone metabolism remains unknown. This study aimed to investigate the molecular mechanisms underlying the effect of 3 '-SL on bone homeostasis. Treatment of human bone marrow stromal cells (hBMSCs) with 3 '-SL enhanced osteogenic differentiation and inhibited adipogenic differentiation of hBMSCs. RNA sequencing showed that 3 '-SL enhanced laminin subunit gamma-2 expression and promoted osteogenic differentiation via the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Furthermore, 3 '-SL inhibited the receptor activator of nuclear factor kappa B ligand-induced osteoclast differentiation of bone marrow-derived macrophages through the nuclear factor kappa B and mitogen-activated protein kinase signaling pathway, ameliorated osteoporosis in ovariectomized mice, and positively regulated bone remodeling. Our findings suggest 3 '-SL as a potential drug for osteoporosis. 3 '-Sialyllactose alleviates the progression of osteoporosis by regulating bone homeostasis and may have a therapeutic effect as an anti-osteoporosis agent.