title: Nuclear receptor retinoid-related orphan receptor α1 modulates the metabolic activity of human osteoblasts.
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 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.
authors.affiliation: Orthopaedics Research Laboratory, Research Centre, Hôpital du Sacré-Coeur de Montréal, University of Montreal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5. mohamed.benderdour@umontreal.ca
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
authors.forename: Hassan
authors.initials: H
authors.lastname: Fahmi
authors.forename: François
authors.initials: F
authors.lastname: Beaudet
authors.forename: Julio C
authors.initials: JC
authors.lastname: Fernandes
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D002113:Calcification, Physiologic / Q000502:physiology; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D024042:Collagen Type I; D016328:NF-kappa B; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000469:Alkaline Phosphatase; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone