A novel promoter regulates calcitonin receptor gene expression in human osteoclasts.
The 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.
Shen
Zhenxin
Z
New England Baptist Bone and Joint Institute, Boston, MA 02120, USA. zshen@bidmc.harvard.edu
Crotti
Tania N
TN
Flannery
Merrilee R
MR
Matsuzaki
Kenichiro
K
Goldring
Steven R
SR
McHugh
Kevin P
KP
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger; D018003:Receptors, Calcitonin / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection
D053245:RANK Ligand; D012333:RNA, Messenger; D018003:Receptors, Calcitonin