Nuclear receptor retinoid-related orphan receptor α1 modulates the metabolic activity of human osteoblasts

✍ Scribed by Mohamed Benderdour; Hassan Fahmi; François Beaudet; Julio C. Fernandes; Qin Shi

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 915 KB
• Volume: 112
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.23141

✦ Synopsis

Nuclear receptor retinoid-related orphan receptor alpha (RORa1) 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 RORa1 in human MG-63 osteoblast-like cells. Reverse transcriptase-polymerase chain reaction and immunocytochemical analysis revealed that human MG-63 osteoblasts expressed and produced RORa1. Other cell lines, such as THP-1 monocytes expressed also RORa1. RORa1 over-expression increased alkaline phosphatase, osteocalcin, cell mineralization, and collagen type I mRNA and protein expression, while RORa1 RNA silencing inhibited these responses. In addition, RORa1 over-expression suppressed the tumor necrosis factor-alpha (TNFa)-induced production of cyclooxygenase-2, prostaglandin E 2 , and metalloproteinase-9. Examination of the signaling pathways disclosed that RORa1 was able to block TNFa-evoked nuclear factor-kappaB activation. In conclusion, this study demonstrates that RORa1 is involved in human osteoblast metabolism by stimulating osteoblast marker expression and inhibiting inflammatory responses. The results may encourage further exploration of RORa1 as a potential target for the treatment of bone disorders related to inflammation.