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

Authors

  • Mohamed Benderdour,

    Corresponding author
    1. Orthopaedics Research Laboratory, Research Centre, Hôpital du Sacré-Coeur de Montréal, University of Montreal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5
    • Orthopaedics Research Laboratory, Research Centre, Hôpital du Sacré-Cœur de Montréal, University of Montreal, 5400 Gouin Blvd. W., Montreal, Quebec, Canada H4J 1C5.
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  • Hassan Fahmi,

    1. Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center, Notre-Dame Hospital, Montreal, Quebec, Canada
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  • François Beaudet,

    1. Department of Rheumatology, Hôpital du Sacré-Cœur de Montréal, University of Montreal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5
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  • Julio C. Fernandes,

    1. Orthopaedics Research Laboratory, Research Centre, Hôpital du Sacré-Coeur de Montréal, University of Montreal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5
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  • Qin Shi

    1. Orthopaedics Research Laboratory, Research Centre, Hôpital du Sacré-Coeur de Montréal, University of Montreal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5
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Abstract

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 E2, 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.

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