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| miR-34a调节骨稳态在骨质疏松中的应用前景 |
| The modulating effect of miR-34a on bone homeostasis ： potential implication in osteoporosis |
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| DOI：10.3969/j.issn.1006.7108.2015.07.026 |
| 中文关键词: miR-34a 骨稳态 骨质疏松 |
| 英文关键词:miR-34a bone homeostasis osteoporosis |
| 基金项目:广东省教育厅学科建设专项基金（育苗工程）（2013 LYM-0012 )；广州中医药大学优秀青年学者科研基金项目 (KAB110133K04);广东省科技厅资助项目（2012B031800208);广东省自然科学基金项目（S2013010015870) |
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| 中文摘要: |
| miR-34a是一个非编码蛋白的单链小分子RNA，在转录水平上通过碱基配对3’-端非翻译区域抑制靶基因表达，多用于肿瘤学的研究中，可通过下调原癌基因的表达抑制肿瘤细胞生长，近年发现其参与骨代谢过程中骨稳态的调节。Tgif2通过与 DNA结合或与TGFβ激活的Smads相互作用抑制TGFP基因表达而抑制成骨细胞的增殖，且Tgif2与RNAKL通路形成一个正反馈循环，RNAKL通路诱导的转录因子增加Tgif2活性，Tgif2又反过来促进RNAKL通路中转导因子的活性，从而促进破骨细胞的生长分化，miR-34a主要通过下调Tgif2基因的表达，促进成骨细胞增殖，且miR-34a下调Tgif2表达时，也间接抑制了 OPG/RANK/RANKL通路的转导，抑制破骨细胞增殖、分化。同时MiR-34a是肿瘤抑制基因P53最常见的转录靶点，P53不仅在转录水平对miR-34a进行调节，而且影响miR-34a前体形成和成熟。P53、miR-34a及Tgif2三者相互作用，直接影响成骨破骨细胞的增殖与分化，且与多个经典信号通路均有交叉，如OPG/RANK/RANKL通路、Wnt/hatenin经典信号通路，参与经典通路中相关因子的调节，间接影响骨稳态。因此，研究miR-34a如何调节成骨破骨分化及协调细胞内其他调节通路共同维持骨稳态将会成为防治骨质疏松症的重要研究方向。 |
| 英文摘要: |
| miR-34a is a non-coding，single-stranded small RNA，which inhibits gene expression at the post-transcriptional level through nucleotide base pairing between complementary sequences of miRNAs and 3 ’ -untranslated regions of messenger RNAs ( mRNAs ) . It has been demonstrated to function as a tumor suppressor by down-regulating the expression of many essential oncogenes and therefore it is often used in the studies of oncology. Recently it has been found to be involved in the regulation of bone homeostasis. Tgif2 has been reported to represses osteoblast proliferation by binding directly to DNA or interacts with TGF β- activated Smads. Tgif2 intensifies osteoclastogenesis through a positive feedback loop in which RANKL-induced transcription factors activate Tgif2 expression，and Tgif2 in turn promotes their activity. MiR-34a facilitates osteogenesis by down -regulating Tgif2 expression and restrains osteoclastogenesis by indirectly suppressing OPG/RANK RANKL signal pathway while down-regulating Tgif2. Meanwhile，miR-34a is a direct transcriptional target of the tumor suppressor p53 that mediates genetic transcription of miR- 34a and their form of pre-miRNA. The interaction of miR-34a，Tgif2，and P53 regulates bone homeostasis directly through affecting proliferation and differentiation of osteoblasts and osteoclasts. The action indirectly affects bone homeostasis by involving many factors in the classical signal pathways and by crosslinking with OPG/RANWRANKL and Wnt/β-catenin signal pathways. Therefore，it is meaningful to investigate how miR-34 regulates osteoblast and osteoclast differentiation and how it interacts with other signal pathways to modulate bone homeostasis. |
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