Nuclear receptor retinoid-related orphan receptor α1 modulates the metabolic activity of human osteoblasts
| Autor: | Qin Shi, Julio Cesar B. Fernandes, Hassan Fahmi, François Beaudet, Mohamed Benderdour |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Osteocalcin Biology Biochemistry Collagen Type I Dinoprostone Calcification Physiologic Cell Line Tumor Internal medicine medicine Humans Receptor Molecular Biology Inflammation Orphan receptor Osteoblasts Tumor Necrosis Factor-alpha NF-kappa B Nuclear Receptor Subfamily 1 Group F Member 1 Osteoblast Cell Biology Alkaline Phosphatase Antigens Differentiation Neuron-derived orphan receptor 1 Cell biology Endocrinology medicine.anatomical_structure Gene Expression Regulation Matrix Metalloproteinase 9 Nuclear receptor Cyclooxygenase 2 biology.protein Tumor necrosis factor alpha Signal transduction |
| Zdroj: | Journal of Cellular Biochemistry. 112:2160-2169 |
| ISSN: | 0730-2312 |
| DOI: | 10.1002/jcb.23141 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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