| Summary: | Osteoporosis is a leading world health problem that results from an imbalance between bone formation and bone resorption. β-glucans has been extensively reported to exhibit a wide range of biological activities, including antiosteoporosis both in vitro and in vivo. However, the molecular mechanisms responsible for β-glucan-mediated bone formation in osteoblasts have not yet been investigated. The oyster mushroom <i>Pleurotus sajor-caju</i> produces abundant amounts of an insoluble β-glucan, which is rendered soluble by enzymatic degradation using <i>Hevea</i> glucanase to generate low-molecular-weight glucanoligosaccharide (<i>Ps</i>-GOS). This study aimed to investigate the osteogenic enhancing activity and underlining molecular mechanism of <i>Ps</i>-GOS on osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. In this study, it was demonstrated for the first time that low concentrations of <i>Ps</i>-GOS could promote cell proliferation and division after 48 h of treatment. In addition, <i>Ps</i>-GOS upregulated the mRNA and protein expression level of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), which are both involved in BMP signaling pathway, accompanied by increased alkaline phosphatase (ALP) activity and mineralization. <i>Ps</i>-GOS also upregulated the expression of osteogenesis related genes including ALP, collagen type 1 (COL1), and osteocalcin (OCN). Moreover, our novel findings suggest that <i>Ps</i>-GOS may exert its effects through the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways.
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