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Abstract
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 Pleurotus sajor-caju produces abundant amounts of an insoluble β-glucan, which is rendered soluble by enzymatic degradation using Hevea glucanase to generate low-molecular-weight glucanoligosaccharide (Ps-GOS). This study aimed to investigate the osteogenic enhancing activity and underlining molecular mechanism of Ps-GOS on osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. In this study, it was demonstrated for the first time that low concentrations of Ps-GOS could promote cell proliferation and division after 48 h of treatment. In addition, Ps-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. Ps-GOS also upregulated the expression of osteogenesis related genes including ALP, collagen type 1 (COL1), and osteocalcin (OCN). Moreover, our novel findings suggest that Ps-GOS may exert its effects through the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways.
Highlights
Osteoporosis is a global disease resulting from an imbalance of bone homeostasis
We show that Pleurotus sajor-caju glucanoligosaccharide (Ps-GOS) promotes MC3T3-E1 cell proliferation, and induction of bone morphogenetic protein-2 (BMP-2) and Runx-2, which act coordinately, together with components of mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways, to enhance both gene expression of osteogenic bone markers and mineralization
Only concentrations in the range 0.001 to 10 μg/mL were used in further experiments. This results indicated that low concentrations of Ps-GOS stimulate osteoblast proliferation without toxicity
Summary
Osteoporosis is a global disease resulting from an imbalance of bone homeostasis. An increase in the ratio of bone resorption to bone formation causes low bone mass and strength, which leads to increased fragility and susceptibility to fracture [1]. The disease occurs in older (>50 year) men and women [2], with increased likelihood in post-menopausal women. The latter effect is due to the absence of estrogen [3], which plays a crucial role in maintaining bone metabolic balance in bone homeostasis [4,5]. An imbalance involving an increase in bone resorption and/or a decrease in bone formation can cause osteoporosis [7]
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