Nuclear Receptor Retinoid-Related Orphan Receptor α1 Modulates the Metabolic Activity of Human Osteoblasts

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.