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Expression of the calcitonin receptor, calcitonin receptor‐like receptor, and receptor activity modifying proteins during osteoclast differentiation
Author(s) -
Granholm Susanne,
Lundberg Pernilla,
Lerner Ulf H.
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21674
Subject(s) - calcitonin receptor , enzyme linked receptor , receptor , interleukin 21 receptor , osteoclast , calcitonin , 5 ht5a receptor , chemistry , estrogen related receptor gamma , microbiology and biotechnology , endocrinology , medicine , biology , calcitonin gene related peptide , biochemistry , nuclear receptor , neuropeptide , gene , transcription factor
Abstract The expressions of the calcitonin receptor (CTR), the calcitonin receptor‐like receptor (CLR), the receptor activity‐modifying proteins (RAMP) 1–3, and of the receptor component protein (RCP) have been studied in mouse bone marrow macrophages (BMM) during osteoclast differentiation, induced by treatment with M‐CSF and RANKL. Analyses of mRNA showed that CLR and RAMP1–3, but not CTR, were expressed in M‐CSF stimulated BMM. RANKL gradually increased CTR mRNA, transiently enhanced CLR and transiently decreased RAMP1 mRNA, but did not affect RAMP2, RAMP3, or RCP mRNA. However, RANKL did not affect protein levels of CLR or RAMP1–3 as assessed by Western blots or FACS analyses, whereas immunocytochemistry showed enhanced CTR protein. Analyses of cAMP production showed that BMM cells expressed functional receptors for calcitonin gene‐related peptide (CGRP), amylin, adrenomedullin, and intermedin, but not for calcitonin and calcitonin receptor stimulating peptide (CRSP), but that RANKL induced the expression of receptors for calcitonin and CRSP as well. Calcitonin, CGRP, amylin, adrenomedullin, intermedin, and CRSP all down regulated the CTR mRNA, but none of the peptides caused any effects on the expression of CLR or any of the RAMPs. Our data show that BMM cells express receptors for CGRP, amylin, adrenomedullin, and intermedin and that RANKL induces the formation of receptors for calcitonin and CRSP in these cells. We also show, for the first time, that the CTR is not only down regulated by signaling through the CTR but also by the peptides signaling through CLR/RAMPs. J. Cell. Biochem. 104: 920–933, 2008. © 2008 Wiley‐Liss, Inc.