Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice

Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is a potential strategy for the treatment of osteoporosis (OP). Naturally derived oligosaccharides have shown significant anti-osteoporotic effects. N...

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Main Authors: Qi Zhang, Sijing Hu, Jianjun Wu, Peng Sun, Quanlong Zhang, Yang Wang, Qiming Zhao, Ting Han, Luping Qin, Qiaoyan Zhang
Format: Article
Language:English
Published: Tsinghua University Press 2023-03-01
Series:Food Science and Human Wellness
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213453022001781
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author Qi Zhang
Sijing Hu
Jianjun Wu
Peng Sun
Quanlong Zhang
Yang Wang
Qiming Zhao
Ting Han
Luping Qin
Qiaoyan Zhang
author_facet Qi Zhang
Sijing Hu
Jianjun Wu
Peng Sun
Quanlong Zhang
Yang Wang
Qiming Zhao
Ting Han
Luping Qin
Qiaoyan Zhang
author_sort Qi Zhang
collection DOAJ
description Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is a potential strategy for the treatment of osteoporosis (OP). Naturally derived oligosaccharides have shown significant anti-osteoporotic effects. Nystose (NST), an oligosaccharide, was isolated from the roots of Morinda officinalis How. (MO). The aim of the present study was to investigate the effects of NST on bone loss in ovariectomized mice, and explore the underlying mechanism of NST in promoting differentiation of BMSCs to osteoblasts. Administration of NST (40, 80 and 160 mg/kg) and the positive control of estradiol valerate (0.2 mg/kg) for 8 weeks significantly prevented bone loss induced by ovariectomy (OVX), increased the bone mass density (BMD), improved the bone microarchitecture and reduced urine calcium and deoxypyridinoline (DPD) in ovariectomized mice, while inhibited the increase of body weight without significantly affecting the uterus weight. Furthermore, we found that NST increased osteogenic differentiation, inhibited adipogenic differentiation of BMSCs in vitro, and upregulated the expression of the key proteins of BMP and Wnt/β-catenin pathways. In addition, Noggin and Dickkopf-related protein-1 (DKK-1) reversed the effect of NST on osteogenic differentiation and expression of the key proteins in BMP and Wnt/β-catenin pathway. The luciferase activities and the molecular docking analysis further supported the mechanism of NST. In conclusion, these results indicating that NST can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.
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publishDate 2023-03-01
publisher Tsinghua University Press
record_format Article
series Food Science and Human Wellness
spelling doaj-art-68e3c1ea6d7748c589c164c1dffb04062025-02-03T04:06:19ZengTsinghua University PressFood Science and Human Wellness2213-45302023-03-01122634646Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized miceQi Zhang0Sijing Hu1Jianjun Wu2Peng Sun3Quanlong Zhang4Yang Wang5Qiming Zhao6Ting Han7Luping Qin8Qiaoyan Zhang9School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaZhejiang Traditional Chinese Medicine & Health Industry Group Co., Ltd. Hangzhou 310016, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmacy, Second Military Medical University, Shanghai 200433, China; Corresponding authors.School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Corresponding authors.School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Corresponding authors.Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is a potential strategy for the treatment of osteoporosis (OP). Naturally derived oligosaccharides have shown significant anti-osteoporotic effects. Nystose (NST), an oligosaccharide, was isolated from the roots of Morinda officinalis How. (MO). The aim of the present study was to investigate the effects of NST on bone loss in ovariectomized mice, and explore the underlying mechanism of NST in promoting differentiation of BMSCs to osteoblasts. Administration of NST (40, 80 and 160 mg/kg) and the positive control of estradiol valerate (0.2 mg/kg) for 8 weeks significantly prevented bone loss induced by ovariectomy (OVX), increased the bone mass density (BMD), improved the bone microarchitecture and reduced urine calcium and deoxypyridinoline (DPD) in ovariectomized mice, while inhibited the increase of body weight without significantly affecting the uterus weight. Furthermore, we found that NST increased osteogenic differentiation, inhibited adipogenic differentiation of BMSCs in vitro, and upregulated the expression of the key proteins of BMP and Wnt/β-catenin pathways. In addition, Noggin and Dickkopf-related protein-1 (DKK-1) reversed the effect of NST on osteogenic differentiation and expression of the key proteins in BMP and Wnt/β-catenin pathway. The luciferase activities and the molecular docking analysis further supported the mechanism of NST. In conclusion, these results indicating that NST can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.http://www.sciencedirect.com/science/article/pii/S2213453022001781NystoseBone marrow mesenchymal stem cellOsteoblastAdipocyteBMP pathwayWnt/β-catenin pathway
spellingShingle Qi Zhang
Sijing Hu
Jianjun Wu
Peng Sun
Quanlong Zhang
Yang Wang
Qiming Zhao
Ting Han
Luping Qin
Qiaoyan Zhang
Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice
Food Science and Human Wellness
Nystose
Bone marrow mesenchymal stem cell
Osteoblast
Adipocyte
BMP pathway
Wnt/β-catenin pathway
title Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice
title_full Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice
title_fullStr Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice
title_full_unstemmed Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice
title_short Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice
title_sort nystose attenuates bone loss and promotes bmscs differentiation to osteoblasts through bmp and wnt β catenin pathway in ovariectomized mice
topic Nystose
Bone marrow mesenchymal stem cell
Osteoblast
Adipocyte
BMP pathway
Wnt/β-catenin pathway
url http://www.sciencedirect.com/science/article/pii/S2213453022001781
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