Resveratrol alleviates osteoporosis through improving the osteogenic differentiation of bone marrow mesenchymal stem cells

X.-H. Chen, Z.-G. Shi, H.-B. Lin, F. Wu, F. Zheng, C.-F. Wu, M.-W. Huang

Department of Orthopedics, the Affiliated Hospital of Putian University; Affiliated Hospital of Putian University Teaching Hospital of Fujian Medical University; Affiliated Putian Hospital of Southern Medical University; Putian, China. 1552279981@qq.com

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• Pharmacology

OBJECTIVE: To investigate the protective effect of Resveratrol (RES) on TNF-α-induced inhibition of osteogenic differentiation, thus alleviating the progression of osteoporosis (OP).

MATERIALS AND METHODS: OP model in rats was first conducted by performing ovariectomy (OVX). Rats were randomly divided into sham group, OVX group, and RES+OVX group. Body weight of each rat was regularly recorded every week. Bone mineral density (BMD) of rat femoral metaphysis was measured by micro-CT. Changes in radial degrees and loads of rat femora were examined through three-point bending experiments. Relative levels of OCN and Runx2 in each group were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Alkaline phosphatase (ALP) activity and calcification ability were assessed through ALP staining and alizarin red staining, respectively. Bone mesenchymal stem cells (BMSCs) were extracted from healthy rats and divided into control group, Tumor necrosis factor-α (TNF-α) group, RES group, and TNF-α+RES group based on different treatments. Relative levels of OCN and Runx2, ALP activity, and calcification ability in each group were detected in the same way. Finally, protein levels of NF-κB and β-catenin in BMSCs were determined.

RESULTS: Rats in each group gained body weight during the experimental period, especially those in OVX group and RES+OVX group. No significant difference in the body weight was found between OVX group and RES+OVX group. BMD in rat femora of RES+OVX group was higher than in OVX group but lower than sham group. Elastic/max radial degree and elastic/max load of femora were markedly reduced in OVX group compared to RES+OVX group. Relative levels of OCN and Runx2, ALP activity and calcification ability decreased in OVX group relative to sham group, which were partially reversed by RES treatment. After osteogenic differentiation in BMSCs induced with TNF-α, viability and calcification ability were markedly reduced and were upregulated by RES treatment. Moreover, RES treatment enhanced the downregulated levels of OCN and Runx2 in BMSCs undergoing TNF-α induction. Upregulated protein levels of nuclear factor kappa-B (NF-κB) and β-catenin in TNF-α-induced BMSCs were downregulated by RES treatment.

CONCLUSIONS: The inhibited osteogenic differentiation of BMSCs undergoing TNF-α induction is improved by resveratrol treatment, which contributes to alleviate the progression of osteoporosis.

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