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.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6352-6359. doi: 10.26355/eurrev_201907_18459.
To investigate the protective effect of Resveratrol (RES) on TNF-α-induced inhibition of osteogenic differentiation, thus alleviating the progression of osteoporosis (OP).
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.
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.
The inhibited osteogenic differentiation of BMSCs undergoing TNF-α induction is improved by resveratrol treatment, which contributes to alleviate the progression of osteoporosis.
研究白藜芦醇（RES）对 TNF-α诱导的成骨分化抑制的保护作用，从而缓解骨质疏松症（OP）的进展。
首先通过卵巢切除术（OVX）建立大鼠 OP 模型。大鼠随机分为假手术组、OVX 组和 RES+OVX 组。每周定期记录每只大鼠的体重。通过 micro-CT 测量大鼠股骨干骺端的骨密度（BMD）。通过三点弯曲实验检测大鼠股骨的径向程度和载荷的变化。通过定量实时聚合酶链反应（qRT-PCR）测定各组 OCN 和 Runx2 的相对水平。通过碱性磷酸酶（ALP）染色和茜素红染色分别评估 ALP 活性和钙化能力。从健康大鼠中提取骨髓间充质干细胞（BMSCs），根据不同的处理方法分为对照组、肿瘤坏死因子-α（TNF-α）组、RES 组和 TNF-α+RES 组。同样检测各组 OCN 和 Runx2、ALP 活性和钙化能力的相对水平。最后，测定 BMSCs 中 NF-κB 和 β-连环蛋白的蛋白水平。
各组大鼠在实验期间体重增加，特别是 OVX 组和 RES+OVX 组。OVX 组和 RES+OVX 组之间的体重无显著差异。RES+OVX 组大鼠股骨 BMD 高于 OVX 组，但低于假手术组。与 RES+OVX 组相比，OVX 组大鼠股骨的弹性/最大径向度和弹性/最大载荷明显降低。与假手术组相比，OVX 组 OCN 和 Runx2 的相对水平、ALP 活性和钙化能力降低，RES 处理部分逆转。在 TNF-α诱导的 BMSCs 成骨分化后，细胞活力和钙化能力明显降低，RES 处理后上调。此外，RES 处理增强了 TNF-α诱导的 BMSCs 中下调的 OCN 和 Runx2 水平。RES 处理可下调 TNF-α诱导的 BMSCs 中核因子 kappa-B（NF-κB）和 β-连环蛋白的上调蛋白水平。
白藜芦醇处理可改善 TNF-α诱导的 BMSCs 成骨分化抑制，有助于缓解骨质疏松症的进展。
