miR-1307-3p suppresses the chondrogenic differentiation of human adipose-derived stem cells by targeting BMPR2.

miR-1307-3p suppresses the chondrogenic differentiation of human adipose-derived stem cells by targeting BMPR2.
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miR-1307-3p通过靶向BMPR2抑制人脂肪干细胞的软骨分化

DOI:
10.3892/ijmm.2018.3891
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发表时间:
2018-12
影响因子:
5.4
通讯作者:
Tian XB
Tian XB
中科院分区:
医学3区
文献类型:
--
作者:
Yang Z;Li R;Ao J;Wa QD;Zhang Y;Chen L;Wen J;Chen B;Pan W;Li B;Tian XB

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微小RNA(miRs)参与多种生理过程,包括软骨形成分化,然而,它们在人脂肪来源干细胞(hADSCs)软骨形成分化中的表达及作用至今仍有待充分阐明。我们先前的研究通过微阵列和Northern杂交分析表明,在软骨形成分化过程中,miR - 1307 - 3p显著下调。本研究旨在探讨miR - 1307 - 3p对软骨形成分化的影响及其潜在机制。首先,通过逆转录定量聚合酶链反应分析证实了miR - 1307 - 3p表达降低。随后,miR - 1307 - 3p的功能获得和缺失实验表明,miR - 1307 - 3p的过表达抑制了软骨基质蛋白聚糖的沉积,并降低了软骨相关标志物的表达,包括性别决定区Y盒9、II型胶原蛋白α1链和聚集蛋白聚糖,而miR - 1307 - 3p的敲低则具有相反的效果。此外,骨形态发生蛋白受体2型(BMPR2)被确定为miR - 1307 - 3p的一个靶标。进一步的机制研究表明,miR - 1307 - 3p至少部分通过抑制BMPR2 - 母亲抗五体不全蛋白信号通路来减弱hADSCs的软骨形成分化。总之,这些研究结果揭示,miR - 1307 - 3p通过靶向BMPR2及其下游信号通路抑制hADSCs的软骨形成分化,这可能为软骨损伤的治疗提供新的治疗线索。
MicroRNAs (miRs) are involved in several physiological processes, including chondrogenic differentiation, however, their expression and roles in the chondrogenic differentiation of human adipose-derived stem cells (hADSCs) remain to be fully elucidated to date. Our previous study showed that miR-1307-3p was significantly downregulated during chondrogenic differentiation by microarray and northern blot analysis. The present study aimed to investigate the effects of miR-1307-3p on chondrogenic differentiation and the underlying mechanisms. First, the decreased expression of miR-1307-3p was confirmed by reverse transcription-quantitative polymerase chain reaction analysis. Subsequently, gain- and loss-of-function of miR-1307-3p experiments showed that the overexpression of miR-1307-3p suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage-related markers, including sex determining region Y-box 9, collagen type II α1 chain and aggrecan, whereas the knockdown of miR-1307-3p had the opposite effect. In addition, bone morphogenetic protein receptor type 2 (BMPR2) was identified as a target of miR-1307-3p. Further mechanistic investigations showed that miR-1307-3p attenuated the chondrogenic differentiation of hADSCs at least partly by inhibiting BMPR2-mothers against decapentaplegic signaling pathways. In conclusion, the findings revealed that miR-1307-3p inhibited the chondrogenic differentiation of hADSCs by targeting BMPR2 and its down-stream signaling pathway, which may provide novel therapeutic clues for the treatment of cartilage injury.
软骨形成 ATDC5 和脂肪间充质干细胞中 microRNA-92a 的存在和功能
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