The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses
The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses
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MicroRNA-381 在软骨形成和 IL-1-β 诱导软骨细胞反应中的作用
DOI：
10.1159/000430148
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Liao, Weiming
中科院分区：
文献类型：
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作者：
Hou, Changhe;Meng, Fangang;Liao, Weiming
目的：调节软骨降解的分子途径尚不清楚。miR-381被鉴定为软骨形成相关基因的假定调节因子。在这里，我们研究了它在软骨形成和骨关节炎软骨退变中的作用。研究方法：在体外评估miR-381在原代人（PHC）和小鼠（PMC）软骨细胞以及ATDC 5衍生的软骨细胞中响应于IL-1β刺激的表达;以及在体内评估miR-381在小鼠胚胎和人骨关节炎软骨中的表达。分别使用合成的RNA模拟物或抑制剂和荧光素酶测定来评估miR-381对软骨形成和NF-κ B信号传导的影响。使用Sox 9和Runx 2的siRNA或过表达质粒探测miR 381的上游调节子。结果：miR-381在软骨形成和肥大ATDC 5细胞中表达升高。miR-381在体外由ATDC 5细胞、PMC和PHCs中的IL-1β诱导，并且在体内在软骨降解或吸收的区域中表达。过表达Runx 2或Sox 9可增加ATDC 5细胞中miR-381的表达。miR-381抑制II型胶原α 1的表达，并增强金属蛋白酶-13（MMP-13）的表达，但不调节NFKBIA和NKRF活性。结论：miR-381在软骨形成过程中和关节炎软骨中高表达。它可能通过抑制II型胶原和诱导MMP-13而促进软骨基质的吸收。
Aim: The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration. Methods: miR-381 expression was assessed in vitro in response to IL-1β stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2. Results: miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1β in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity. Conclusion: miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13.