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Nuclear receptor retinoid‐related orphan receptor α1 modulates the metabolic activity of human osteoblasts
Author(s) -
Benderdour Mohamed,
Fahmi Hassan,
Beaudet François,
Fernandes Julio C.,
Shi Qin
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23141
Subject(s) - orphan receptor , nuclear receptor , osteoblast , endocrinology , osteocalcin , medicine , chemistry , retinoid x receptor alpha , small interfering rna , signal transduction , microbiology and biotechnology , receptor , runx2 , tumor necrosis factor alpha , alkaline phosphatase , transcription factor , biology , rna , biochemistry , enzyme , in vitro , gene
Nuclear receptor retinoid‐related orphan receptor alpha (RORα1) 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 RORα1 in human MG‐63 osteoblast‐like cells. Reverse transcriptase‐polymerase chain reaction and immunocytochemical analysis revealed that human MG‐63 osteoblasts expressed and produced RORα1. Other cell lines, such as THP‐1 monocytes expressed also RORα1. RORα1 over‐expression increased alkaline phosphatase, osteocalcin, cell mineralization, and collagen type I mRNA and protein expression, while RORα1 RNA silencing inhibited these responses. In addition, RORα1 over‐expression suppressed the tumor necrosis factor‐alpha (TNFα)‐induced production of cyclooxygenase‐2, prostaglandin E 2 , and metalloproteinase‐9. Examination of the signaling pathways disclosed that RORα1 was able to block TNFα‐evoked nuclear factor‐kappaB activation. In conclusion, this study demonstrates that RORα1 is involved in human osteoblast metabolism by stimulating osteoblast marker expression and inhibiting inflammatory responses. The results may encourage further exploration of RORα1 as a potential target for the treatment of bone disorders related to inflammation. J. Cell. Biochem. 112: 2160–2169, 2011. © 2011 Wiley‐Liss, Inc.