HOTAIRM1 promotes osteogenic differentiation and alleviates osteoclast differentiation by inactivating the NF-κB pathway
HOTAIRM1 promotes osteogenic differentiation and alleviates osteoclast differentiation by inactivating the NF-κB pathway
复制标题
HOTAIRM1 通过失活 NF-κB 途径促进成骨分化并减轻破骨细胞分化。
DOI：
10.1093/abbs/gmaa164
复制
发表时间：
2021-01-06
影响因子：
3.7
通讯作者：
Hong, Wei
中科院分区：
文献类型：
--
作者：
Ren, Yi;Zhang, Kun;Hong, Wei
骨质疏松症(OP)是最常见的慢性进行性骨病之一，由成骨细胞骨形成不足或破骨细胞过度骨吸收引起，继而增加骨折的风险。越来越多的证据表明，长非编码RNA(LncRNAs)在许多生物过程和各种疾病中发挥着关键作用。然而，HOX反义基因间核糖核酸髓系1(HOTAIRM1)在破骨细胞分化、成骨分化和骨质疏松症中的作用和机制尚不清楚。在本研究中，我们发现HOTAIRM1在黄韧带骨化和成骨分化过程中上调，而在破骨细胞分化和OP的人和小鼠骨和血清中表达下调。进一步的研究表明，沉默Hotairm1降低了成骨标志物的表达，并减弱了成骨作用。此外，强制表达Hotairm1抑制了破骨细胞生成标志物的表达，减轻了核因子-kappa B受体激活剂(NE-kappa B)配体(RANKL)诱导的破骨细胞分化。从机制上讲，Hotairm1抑制了p65和kappa Bα抑制因子的磷酸化。(I kappa Bα)和减弱RANKL介导的PHos-p65和I kappa Bα的增强，提示Hotairm1通过NE-kappa B途径抑制RANKL诱导的破骨细胞生成。总之，我们的数据确定了HOTAIRM1在OP中的关键作用，为该分子作为潜在的诊断标记物和可能的治疗靶点提供了证据。
Osteoporosis (OP), one of the most prevalent chronic progressive bone diseases, is caused by deficiency in bone formation by osteoblasts or excessive bone resorption by osteoclasts and subsequently increases the risk of bone fractures. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play key roles in many biological processes and various disorders. However, the role and mechanism of HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), a myeloid-specific lncRNA, in osteoclast differentiation, osteogenic differentiation, and OP remain unclear. In this study, we found that HOTAIRM1 was upregulated during ossification of ligamentum flavum and osteogenic differentiation, while it was downregulated in osteoclast differentiation and in the bone and serum of human and mouse with OP. Further investigation revealed that silencing Hotairm1 decreased the expression of the osteogenic markers and attenuated osteogenesis. Moreover, forced Hotairm1 expression inhibited the expressions of the osteoclastogenesis markers and alleviated receptor activator of nuclear factor kappa B (NE-kappa B) ligand (RANKL)-induced osteoclast differentiation. Mechanically, Hotairm1 repressed the phosphorylation of p65 and inhibitor of kappa B alpha. (I kappa B alpha) and attenuated RANKL-mediated enhancement of phos-p65 and I kappa B alpha, suggesting that Hotairm1 inhibits RANKL-induced osteoclastogenesis through the NE-kappa B pathway. In conclusion, our data identified a crucial role of HOTAIRM1 in OP, providing a proof of this molecule as a potential diagnostic marker and a possible therapeutic target against OP.