视黄酸受体RARs和RXRs在hBMSCs成骨分化调控过程中的功能差异
The functional difference between retinoic acid receptor RARs and RXRs on the regulation of osteogenic differentiation in hBMSCs
  
DOI:10.3969/j.issn.1006-7108.2021.07.002
中文关键词:  骨髓间充质干细胞  成骨分化  视黄酸受体  视黄酸X受体
英文关键词:bone marrow mesenchymal stem cells  osteogenesis  retinoic acid receptors  retinoid X receptors
基金项目:国家自然科学基金(81860166,81260283)
作者单位
曹俊* 郑美蓉 刘建云 吴萍 邬亚华 九江学院基础医学院江西 九江 332000 
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中文摘要:
      目的 探讨视黄酸受体RARs和RXRs对hBMSCs成骨分化的影响及机制。方法 hBMSCs体外培养并诱导成骨分化,茜素红和油红O染色检测诱导14 d细胞成骨与成脂分化状态;qRT-PCR及免疫印迹技术检测成骨成脂标志基因以及相关信号通路基因的表达水平。结果 RARs激动剂ATRA、9CRA和TTNPB上调成骨标志基因RUNX2、OSX及OCN的表达,但下调ALPL和I型胶原的表达并抑制钙化,RARs对钙化的抑制可能与其上调TGFβ/SMAD信号通路有关;RXRs激动剂SR11237对成骨分化无明显影响,但可在成骨诱导环境下上调成脂转录因子CEBPB、CEBPA和PPARG的表达,诱导细胞分化为脂肪细胞。结论 RARs诱导hBMSCs成骨分化但抑制钙化过程,RXRs诱导细胞成脂分化,对成骨分化无明显作用。
英文摘要:
      Objective To investigate the effect of retinoic acid receptors (RARs and RXRs) on osteogenic differentiation of hBMSCs. Methods hBMSCs were cultured and induced into osteoblasts. Alizarin red and Oil red O staining were used to detect the osteogenic and adipogenic differentiation status of hBMSCs. qRT-PCR and Western blotting were used to detect the expression levels of osteogenic and adipogenic marker genes and related signal pathway genes. Results RARs agonists ATRA, 9CRA, and TTNPB up-regulated the expression of osteogenic marker genes RUNX2, OSX, and OCN, but down-regulated the expression of ALPL and type I procollagen and inhibited calcification. The inhibition of calcification by RARs might be related to the up-regulation of TGF β/Smad signaling pathway. RXRs agonist SR11237 had no significant effect on osteogenic differentiation, but up-regulated the expression of adipogenic transcription factors CEBPB, CEBPA, and PPARG in osteogenic induction environment and promoted the differentiation of cells into adipocytes. Conclusion RARs induce osteogenic differentiation of hBMSCs, but inhibit calcification. RXRs have no significant effect on osteogenic differentiation, but induce adipogenic differentiation.
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