Shen, Z.Crotti, T.Flannery, M.Matsuzaki, K.Goldring, S.McHugh, K.2008-10-302008-10-302007Biochimica et Biophysica Acta: international journal of biochemistry and biophysics, 2007; 1769(11-12):659-6670006-30021878-2434http://hdl.handle.net/2440/48110The calcitonin receptor (CTR) is expressed in a wide variety of tissues and cell types. In bone, its expression is restricted to osteoclasts, the cells that mediate bone resorption. The human CTR (hCTR) gene has a complex structural organization that exhibits similarity to the porcine (pCTR) and mouse (mCTR) CTR genes. In these species, alternative splicing of a single gene generates multiple CTR isoforms that are distributed in both tissue-specific and species-specific patterns. However, the structural organization of the 5' putative regulatory region and transcriptional mechanisms responsible for tissue-specific expression of the different CTR isoforms are not fully defined. The present studies were undertaken to characterize the structural organization of the 5'-region of the hCTR and identify the regulatory regions involved in osteoclast-specific transcriptional activation. Analysis of mRNA prepared from human osteoclasts using reverse transcription-polymerase chain reaction (RT-PCR) and transient transfection of hCTR promoter-luciferase reporter constructs identified two regions in the 5'-flanking sequence of the hCTR gene that regulated CTR gene expression in osteoclasts. Both of these putative promoters were responsive to the osteoclast-inducing cytokine, receptor activator of NF-kappaB ligand (RANKL) and demonstrated trans-activation by the RANKL-induced transcription factor nuclear factor of activated T cells (NFATc1), consistent with a role in regulating CTR gene expression in osteoclasts.enCells, CulturedOsteoclastsAnimalsHumansMiceReceptors, CalcitoninRNA, MessengerTransfectionGene Expression RegulationTissue DistributionRANK LigandPromoter Regions, GeneticJournal article002008284210.1016/j.bbaexp.2007.08.0052-s2.0-3604900408241868Crotti, T. [0000-0002-5422-3758]