Yang Fenghe, Jia Yusong, Sun Qi, Zheng Chenying, Liu Chuyin, Wang Wei, Du Li, Kang Shengqian, Niu Xufeng, Li Jinyu
Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, P.R. China.
Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing 100083, P.R. China.
Exp Ther Med. 2020 Jul;20(1):309-314. doi: 10.3892/etm.2020.8689. Epub 2020 Apr 27.
Effect of raloxifene (RLF) on the improvement of inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) resulted from tumor necrosis factor-α (TNF-α) induction, thus alleviating the progression of osteoporosis (OP), was investigated. An OP rat model was constructed by performing the procedures of ovariectomy (OVX). Rats were randomly divided into sham group, OVX group and RLF+OVX group. BMSCs were extracted from healthy rats, and randomly divided into control group, TNF-α group, RLF group and TNF-α+RLF group. Viability and cellular calcification ability in each group were detected. The relative levels of osteocalcin (OCN), Runx2 and NF-κB in cells with different treatments were determined. The body weight of rats in the OVX group and RLF+OVX group gradually increased compared with that in the sham group on the 8th week. No significant difference in body weight was observed between the rats of the OVX group and RLF+OVX group. Bone metabolism index (BMD) in the rats of the RLF+OVX group was higher than that of the OVX group, and lower compared with that of the sham group. Compared with the sham group, the elastic/max radial degree and elastic/max load of femora were reduced in the OVX group and RLF+OVX group, especially in the OVX group. The relative levels of OCN and Runx2, as well as the ALP activity and calcification ability, were decreased in the OVX group compared with the sham group, and the effect was partially reversed by the RLF treatment. After osteogenic differentiation of BMSCs, the viability and calcification ability were markedly reduced in TNF-α group, which was reversed by RLF treatment. Moreover, TNF-α induction downregulated the relative levels of OCN and Runx2, and RLF treatment could enhance their levels. The upregulated NF-κB protein level, induced by TNF-α, was reduced after RLF treatment. TNF-α induction inhibits osteogenic differentiation of BMSCs, which could be remarkably alleviated by RLF. It is suggested that RLF contributes to the alleviation of OP progression.
研究了雷洛昔芬（RLF）对改善肿瘤坏死因子-α（TNF-α）诱导导致的骨髓间充质干细胞（BMSCs）成骨分化抑制、从而缓解骨质疏松症（OP）进展的作用。通过卵巢切除术（OVX）构建OP大鼠模型。大鼠随机分为假手术组、OVX组和RLF+OVX组。从健康大鼠中提取BMSCs，并随机分为对照组、TNF-α组、RLF组和TNF-α+RLF组。检测每组的细胞活力和细胞钙化能力。测定不同处理细胞中骨钙素（OCN）、Runx2和NF-κB的相对水平。第8周时，OVX组和RLF+OVX组大鼠的体重与假手术组相比逐渐增加。OVX组和RLF+OVX组大鼠的体重未观察到显著差异。RLF+OVX组大鼠的骨代谢指数（BMD）高于OVX组，但低于假手术组。与假手术组相比，OVX组和RLF+OVX组股骨的弹性/最大径向度和弹性/最大负荷降低，尤其是OVX组。与假手术组相比，OVX组OCN和Runx2的相对水平以及碱性磷酸酶（ALP）活性和钙化能力降低，RLF治疗部分逆转了这种作用。BMSCs成骨分化后，TNF-α组的细胞活力和钙化能力明显降低，RLF治疗可使其逆转。此外，TNF-α诱导下调了OCN和Runx2的相对水平，RLF治疗可提高其水平。TNF-α诱导上调的NF-κB蛋白水平在RLF治疗后降低。TNF-α诱导抑制BMSCs的成骨分化，RLF可显著缓解这种抑制。提示RLF有助于缓解OP进展。
