Nuclear Receptor Retinoid-Related Orphan Receptor α1 Modulates the Metabolic Activity of Human Osteoblasts
Nuclear Receptor Retinoid-Related Orphan Receptor α1 Modulates the Metabolic Activity of Human Osteoblasts
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DOI：
10.1002/jcb.23141
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发表时间：
2011-08-01
影响因子：
4
通讯作者：
Shi, Qin
中科院分区：
文献类型：
--
作者：
Benderdour, Mohamed;Fahmi, Hassan;Shi, Qin
核受体视黄醇相关孤儿受体α(RORα1)是ROR家族受体中的一员。它在胚胎发育的各种组织和器官中广泛表达。然而，到目前为止，人们对其在骨骼中的功能知之甚少。在此，我们阐明了RORα1在人MG-63成骨样细胞中的表达和功能。逆转录聚合酶链式反应和免疫细胞化学分析表明，人MG-63成骨细胞表达并产生RORα1。其他细胞系，如THP-1单核细胞也表达RORα1。RORα1过表达增加碱性磷酸酶、骨钙素、细胞矿化和I型胶原的mRNA和蛋白表达，而RORα1 RNA沉默则抑制这些反应。此外，RoRα1过表达抑制了肿瘤坏死因子-α(TNFα)诱导的环氧合酶-2、前列腺素E(2)和金属蛋白酶-9的产生。对这些信号通路的研究发现，RoRα1能够阻断肿瘤坏死因子α诱导的核因子-kappaB的激活。综上所述，本研究证明RORα1通过刺激成骨细胞标志物的表达和抑制炎症反应参与了人成骨细胞的代谢。这一结果可能会鼓励进一步探索RoRα1作为治疗与炎症相关的骨病的潜在靶点。J.细胞。生物化学。112：2160-2169,2011。(C)2011年Wiley-Liss，Inc.
Nuclear receptor retinoid-related orphan receptor alpha (ROR alpha 1) is a member of ROR-family receptors. It is broadly expressed in various tissues and organs during embryonic development. However, so far, little is known about its function in bone. Here, we have elucidated the expression and function of ROR alpha 1 in human MG-63 osteoblast-like cells. Reverse transcriptase-polymerase chain reaction and immunocytochemical analysis revealed that human MG-63 osteoblasts expressed and produced ROR alpha 1. Other cell lines, such as THP-1 monocytes expressed also ROR alpha 1. ROR alpha 1 over-expression increased alkaline phosphatase, osteocalcin, cell mineralization, and collagen type I mRNA and protein expression, while ROR alpha 1 RNA silencing inhibited these responses. In addition, ROR alpha 1 over-expression suppressed the tumor necrosis factor-alpha (TNF alpha)-induced production of cyclooxygenase-2, prostaglandin E(2), and metalloproteinase-9. Examination of the signaling pathways disclosed that ROR alpha 1 was able to block TNF alpha-evoked nuclear factor-kappaB activation. In conclusion, this study demonstrates that ROR alpha 1 is involved in human osteoblast metabolism by stimulating osteoblast marker expression and inhibiting inflammatory responses. The results may encourage further exploration of ROR alpha 1 as a potential target for the treatment of bone disorders related to inflammation. J. Cell. Biochem. 112: 2160-2169, 2011. (C) 2011 Wiley-Liss, Inc.