In vitro and in silico anti-osteoporosis activities and underlying mechanisms of a fructan, ABW90-1, from Achyranthes bidentate

Achyranthes bidentata is a traditional Chinese medicine used to treat osteoporosis. AB90, a crude saccharide from A. bidentata, showed excellent osteoprotective effects in ovariectomized rats, and ABW90-1, an oligosaccharide purified from AB90, stimulated significant differentiation of osteoblasts....

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Published in:Carbohydrate polymers 2022-01, Vol.276, p.118730-118730, Article 118730
Main Authors: Li, Tianyu, Hou, Xin, Huang, Yihua, Wang, Changsheng, Chen, Haiyun, Yan, Chunyan
Format: Article
Language:English
Subjects:
Achyranthes - chemistry
Achyranthes bidentate
Animals
beta Catenin - metabolism
Bone Morphogenetic Protein 2 - metabolism
Cell Differentiation - drug effects
Cell Line
Cell Proliferation - drug effects
Fructans - analysis
Fructans - pharmacology
Mechanisms
Mice
Molecular docking
Molecular Docking Simulation - methods
Oligosaccharide
Osteoblasts - drug effects
Osteogenesis - drug effects
Osteogenic effects
Osteoporosis
Osteoporosis - metabolism
Rats
Smad1 Protein - metabolism
Wnt Signaling Pathway - drug effects
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Summary:Achyranthes bidentata is a traditional Chinese medicine used to treat osteoporosis. AB90, a crude saccharide from A. bidentata, showed excellent osteoprotective effects in ovariectomized rats, and ABW90-1, an oligosaccharide purified from AB90, stimulated significant differentiation of osteoblasts. However, the osteogenic effects and underlying mechanisms of ABW90-1 have remained unknown. In the present study, we found that ABW90-1 significantly promoted ALP activity, mineralization, and the expression of osteogenic markers in MC3T3-E1 cells. ABW90-1 showed strong binding with the WNT signaling complex and BMP2 based on number of interactions, hydrogen bond length, and binding energy in silico. ABW90-1 significantly increased the expression of active-β-catenin, p-GSK-3β, LEF-1, BMP2, and p-SMAD1. Importantly, the osteogenic effects of ABW90-1 were partially suppressed by DKK-1 and Noggin, which are specific inhibitors of the WNT and BMP signaling pathways, respectively. Collectively, these findings suggest that ABW90-1 has osteogenic effects through crosstalk between WNT/β-catenin and BMP2/SMAD1 signaling pathways. [Display omitted] •ABW90-1 promotes ALP activity and mineralization comparable with that of E2.•ABW90-1 increases the expression levels of osteogenic-related markers.•ABW90-1 strongly binds with the WNT signaling complex and BMP2 in silico.•ABW90-1 activates both WNT/β-catenin and BMP2/SMAD1 signaling pathways.•ABW90-1 may represent a potential strategy for the treatment of osteoporosis.
ISSN:0144-8617
1879-1344
DOI:10.1016/j.carbpol.2021.118730