微小RNA在骨质疏松症治疗中的作用及机制的研究进展
Research advance and mechanism of miRNA in the treatment of osteoporosis
  
DOI:10.3969/j.issn.1006-7108.2016.06.027
中文关键词:  miRNA  信号通路  骨再生  骨质疏松
英文关键词:miRNA  Signal pathway  Bone regeneration  Osteoporosis
基金项目:国家自然科学基金青年科学基金项目(81300710)
作者单位
陈煦1 王新力1 邹远康1 李天1, 2 * 赵雄1* 1. 第四军医大学西京医院骨科西安 710032 2. 第四军医大学生物医学工程学院西安 710032 
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中文摘要:
      骨质疏松症是以骨量减少、骨强度下降、骨折危险性增加为特征,受遗传因素和环境因素共同影响的一种全身骨代谢障碍的疾病。骨质疏松是骨折的重要原因之一,它影响骨折的处理及其预后。原发性骨质疏松症的防治主要包括物理治疗和药物治疗两个方面,物理治疗包括运动疗法和物理因子疗法;药物治疗包括雌激素代替疗法、降钙素、选择性雌激素受体调节剂以及双膦酸盐等,这些药物可以阻止骨吸收但对骨形成的作用影响较小。微小RNA(miRNA)是一种由高等真核生物基因组编码,在进化上十分保守的非编码小分子RNA,具有调控基因表达的能力。miRNA主要通过和靶基因mRNA碱基配对,引导沉默复合体降解mRNA或抑制其翻译。基于miRNA的作用机制,通过人工合成miRNA拟似物和miRNA抑制剂调节miRNA相关通路,或人工构建miRNA介导RNA干扰途径,进行基因和分子治疗,从而在分子水平上为研究新一代基因药物和生物治疗手段提供新的切入点。关于骨质疏松,目前研究发现miRNA主要通过影响Runx2和Osterix信号通路发挥调控成骨信号作用,因此,干预miRNA可通过影响干细胞骨再生延缓骨质疏松进程,促进骨折修复。本文重点对微小RNA在骨分化和骨再生的分子机制及治疗应用做一综述,旨在为骨质疏松的基础研究和临床治疗提供参考。
英文摘要:
      Osteoporosis is a disease of bone metabolism dysfunction in the whole body, characterized by a decrease of bone mass and bone strength, and an increase of fracture risk. Osteoporosis is one of the most important causes of fracture, which affects the treatment and prognosis of fractures. The prevention and treatment of osteoporosis include physical therapy and drug therapy. Physical therapy includes exercise therapy and physical factor therapy. Drug therapy includes estrogen replacement therapy, calcitonin, selective estrogen receptor modulators, and bisphosphonates, etc. These drugs can prevent bone resorption but have little effect on bone formation. miRNA is a highly conserved non-encoding small molecule RNA, which has the ability to regulate gene expression. miRNA is mainly directed to the mRNA base pairing of target genes, leading to the degradation of mRNA or inhibition of translation of the silent complex. Based on the mechanism of miRNA, genes and molecular therapy can be conducted by artificial synthesis of miRNA and miRNA inhibitors, or by artificial construction of miRNA interfering RNA pathway, thus providing a new perspective for the study of new generation of gene drugs and biological treatment. The present study of osteoporosis has found that miRNA plays an important role in the regulation of Runx2 and Osterix signaling pathway. Therefore the intervention of miRNA can delay the process of bone regeneration and promote the repair of bone. This review focuses on the molecular mechanism and application of miRNA in bone differentiation and bone regeneration, which provides a reference for the basic research and clinical treatment of osteoporosis.
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