Expression of the calcitonin receptor, calcitonin receptor-like receptor, and receptor activity modifying proteins during osteoclast differentiation
Expression of the calcitonin receptor, calcitonin receptor-like receptor, and receptor activity modifying proteins during osteoclast differentiation
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DOI：
10.1002/jcb.21674
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发表时间：
2008-06-01
影响因子：
4
通讯作者：
Lerner, Ulf H.
中科院分区：
文献类型：
--
作者：
Granholm, Susanne;Lundberg, Pernilla;Lerner, Ulf H.
在用 M-CSF 和 RANKL 处理诱导的破骨细胞分化过程中，研究了小鼠骨髓巨噬细胞 (BMM) 中降钙素受体 (CTR)、降钙素受体样受体 (CLR)、受体活性修饰蛋白 (RAMP) 1-3 和受体成分蛋白 (RCP) 的表达。 mRNA分析显示，在M-CSF刺激的BMM中表达CLR和RAMP1-3，但不表达CTR。 RANKL逐渐增加CTR mRNA，暂时增强CLR并暂时减少RAMP1 mRNA，但不影响RAMP2、RAMP3或RCP mRNA。然而，通过蛋白质印迹或 FACS 分析评估，RANKL 并不影响 CLR 或 RAMP1-3 的蛋白水平，而免疫细胞化学显示 CTR 蛋白增强。 cAMP 产生的分析表明，BMM 细胞表达降钙素基因相关肽 (CGRP)、胰淀素、肾上腺髓质素和 intermedin 的功能性受体，但不表达降钙素和降钙素受体刺激肽 (CRSP) 的功能性受体，但 RANKL 也诱导降钙素和 CRSP 受体的表达。降钙素、CGRP、胰淀素、肾上腺髓质素、intermedin 和 CRSP 均下调 CTR mRNA，但没有一种肽对 CLR 或任何 RAMP 的表达产生任何影响。我们的数据表明，BMM 细胞表达 CGRP、胰淀素、肾上腺髓质素和 intermedin 受体，并且 RANKL 诱导这些细胞中降钙素和 CRSP 受体的形成。我们还首次表明，CTR 不仅受到 CTR 信号传导的下调，而且还受到 CLR/RAMP 肽信号传导的下调。
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.