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Molecular Endocrinology 11 (7): 905-916
Copyright © 1997 by The Endocrine Society

The ERR-1 Orphan Receptor Is a Transcriptional Activator Expressed During Bone Development

Edith Bonnelye1, Jean Marc Vanacker1, Tanja Dittmar, Agnes Begue, Xavier Desbiens, David T. Denhardt, Jane E. Aubin, Vincent Laudet and Brigitte Fournier

Endocrin’os group (E.B., J.M.V., A.B., V.L.), CNRS UMR 319 Mécanismes du développement et de la Cancérisation Institut de Biologie de Lille, 59021 Lille Cedex France, Novartis Pharma AG (T.D., B.F.), K125 9–17, P11002 Basel, Switzerland Department of Biological Sciences (D.T.D.), Rutgers University, Piscataway, New Jersey 08855, Department of Anatomy and Cell Biology (J.E.A.), University of Toronto, Toronto, M5S 1A8 Canada Centre de Biologie Cellulaire du Développement (X.D.) Université des Sciences et Techniques de Lille Villeneuve d’Ascq, France

We studied the expression of estrogen-related receptor ERR-1 during mouse embryonic development. ERR-1 mRNA is present in bones formed by both the endochondral and intramembranous routes, and the onset of its expression coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone. By gel shift analysis we found that ERR-1 binds as a monomer specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are required for efficient ERR-1 binding. In transient transfection assays, ERR-1 acts as a potent transactivator through the SFRE sequence. This effect is cell-specific since ERR-1 activates transcription in the rat osteosarcoma cell line ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2 cells. Notably, the osteopontin (a protein expressed by osteoblasts and released in the bone matrix) gene promoter is a target for ERR-1 transcriptional regulation. Our findings suggest a role for ERR-1 in bone development and metabolism.




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