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芝麻素通过 p38 和 ERK1/2 MAPK 信号通路刺激成骨细胞分化。

Sesamin stimulates osteoblast differentiation through p38 and ERK1/2 MAPK signaling pathways.

机构信息

Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand.

出版信息

BMC Complement Altern Med. 2012 May 30;12:71. doi: 10.1186/1472-6882-12-71.

Abstract

BACKGROUND

Osteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function.

METHOD

Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting.

RESULTS

Sesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19.

CONCLUSIONS

The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.

摘要

背景

骨质疏松症是一个全球性的健康问题,主要影响绝经后妇女。旨在增加骨质疏松症患者骨量的治疗方法落后于针对骨吸收过程的治疗策略的可比研究。芝麻素是芝麻素中的一种主要木质素化合物,具有多种药理作用,但它对骨细胞功能的活性尚不清楚。在此,我们研究了这种木质素对成骨细胞分化和功能的影响。

方法

通过 MTT 和 alamar blue 测定法在 hFOB1.19 中检测细胞毒性和增殖,直至 96 小时的处理。芝麻素处理 24 小时后检测 COL1、ALP、BMP-2、Runx2、OC、RANKL 和 OPG 的基因表达。在第 7、14 和 21 天测定 ALP 活性。对于矿化测定,将 ADSC 培养在含有或不含有芝麻素的成骨培养基中 21 天,然后用茜素红 S 染色。通过 Western blotting 观察 MAPK 信号通路的激活。

结果

芝麻素促进了 hFOB1.19 中 COL1、ALP、OCN、BMP-2 和 Runx2 的基因表达。另一方面,芝麻素能够上调 OPG 并下调 RANKL 基因表达。芝麻素处理后 ALP 活性也显著增加。有趣的是,芝麻素诱导脂肪来源的干细胞(ADSCs)形成矿化结节,如茜素红 S 染色所示;这意味着芝麻素对成骨细胞的祖细胞和定向细胞阶段都具有合成代谢作用。Western blotting 数据显示,芝麻素激活了 hFOB1.19 中 p38 和 ERK1/2 的磷酸化。

结论

数据表明,芝麻素通过激活 p38 和 ERK MAPK 信号通路具有触发成骨细胞分化的能力,并可能通过成骨细胞中 OPG 和 RANKL 的表达间接调节破骨细胞的发育。因此,芝麻素可能是一种有前途的植物化学物质,可开发用于骨质疏松症治疗的补充剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc06/3488317/5ae6d9f23c08/1472-6882-12-71-1.jpg

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