MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression.
MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression.
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MicroRNA-381 通过抑制组蛋白脱乙酰酶 4 表达来调节软骨细胞肥大
DOI：
10.3390/ijms17091377
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发表时间：
2016-08-23
影响因子：
5.6
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Chen W;Sheng P;Huang Z;Meng F;Kang Y;Huang G;Zhang Z;Liao W;Zhang Z
由Runt相关转录因子2（RUNX 2）和基质金属蛋白酶13（MMP 13）调节的软骨细胞肥大是软骨退变和骨关节炎（OA）发病机制中的关键步骤。我们以前证明microRNA-381（miR-381）促进软骨形成过程中MMP 13的表达，并有助于软骨退变;然而，这一过程的机制仍不清楚。在这项研究中，我们观察到miR-381和组蛋白去乙酰化酶4（HDAC 4），一种直接抑制RUNX 2和MMP 13表达的酶，在ATDC 5细胞的软骨形成后期，以及在E16.5小鼠胚胎长骨发育期间的肥大前和肥大软骨细胞中的不同表达。因此，我们研究了这种miRNA是否在软骨形成过程中调节HDAC 4的表达。值得注意的是，miR-381的过表达抑制HDAC 4表达，但促进RUNX 2表达。此外，用miR-381模拟物转染SW 1353细胞抑制了含有HDAC 4的3′-非翻译区（3′-UTR）的报告构建体的活性。相反，用miR-381抑制剂处理产生增加的HDAC 4表达和减少的RUNX 2表达。最后，HDAC 4表达的敲低导致SW 1353细胞中RUNX 2和MMP 13表达增加。总的来说，我们的结果表明，miR-381通过靶向HDAC 4表观遗传地调节MMP 13和RUNX 2的表达，从而表明抑制miR-381来控制软骨细胞肥大和软骨变性的可能性。
Chondrocyte hypertrophy, regulated by Runt-related transcription factor 2 (RUNX2) and matrix metalloproteinase 13 (MMP13), is a crucial step in cartilage degeneration and osteoarthritis (OA) pathogenesis. We previously demonstrated that microRNA-381 (miR-381) promotes MMP13 expression during chondrogenesis and contributes to cartilage degeneration; however, the mechanism underlying this process remained unclear. In this study, we observed divergent expression of miR-381 and histone deacetylase 4 (HDAC4), an enzyme that directly inhibits RUNX2 and MMP13 expression, during late-stage chondrogenesis of ATDC5 cells, as well as in prehypertrophic and hypertrophic chondrocytes during long bone development in E16.5 mouse embryos. We therefore investigated whether this miRNA regulates HDAC4 expression during chondrogenesis. Notably, overexpression of miR-381 inhibited HDAC4 expression but promoted RUNX2 expression. Moreover, transfection of SW1353 cells with an miR-381 mimic suppressed the activity of a reporter construct containing the 3′-untranslated region (3′-UTR) of HDAC4. Conversely, treatment with a miR-381 inhibitor yielded increased HDAC4 expression and decreased RUNX2 expression. Lastly, knockdown of HDAC4 expression resulted in increased RUNX2 and MMP13 expression in SW1353 cells. Collectively, our results indicate that miR-381 epigenetically regulates MMP13 and RUNX2 expression via targeting of HDAC4, thereby suggesting the possibilities of inhibiting miR-381 to control chondrocyte hypertrophy and cartilage degeneration.
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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
影响因子：
--
作者：
Hou, Changhe;Meng, Fangang;Liao, Weiming
通讯作者：
Liao, Weiming
影响因子：
4.8
作者：
Hong, Sohee;Derfoul, Assia;Hall, David J.
通讯作者：
Hall, David J.
影响因子：
4.8
作者：
Bradley, Elizabeth W.;Carpio, Lomeli R.;Westendorf, Jennifer J.
通讯作者：
Westendorf, Jennifer J.
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Minond, Dmitriy;Lauer-Fields, Janelle L.;Fields, Gregg B.
通讯作者：
Fields, Gregg B.