Effects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development
Effects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development
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DOI：
10.1016/s8756-3282(01)00494-x
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发表时间：
2001-08-01
期刊：
影响因子：
4.1
通讯作者：
Reid, IR
中科院分区：
文献类型：
--
作者：
Cornish, J;Callon, KE;Reid, IR
胰淀素和降钙素基因相关肽（CGRP）是在循环中发现的37个氨基酸的同源肽。这两种肽都属于降钙素家族。与降钙素相似，胰淀素和CGRP抑制破骨细胞活性，尽管它们的效力远低于降钙素。已知降钙素作用于破骨细胞发育的后期阶段，抑制定向破骨细胞前体融合形成成熟的多核细胞;然而，降钙素是否在破骨细胞前体形成的早期起作用存在争议。关于胰淀素和CGRP，破骨细胞发育的问题从未被研究过。本研究将解决这些问题。我们研究了降钙素（鲑鱼和大鼠），胰淀素（人和大鼠），和CGRP（人和大鼠）在小鼠骨髓培养物刺激产生破骨细胞使用1 α，25-二羟维生素D-3的影响。当降钙素浓度> 10（-13）mol/L时，抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞和TRAP阳性单核/双核细胞数量呈剂量依赖性减少。胰淀素和降钙素基因相关肽在浓度> 10（-9）mol/L时显示相似的作用。此外，降钙素显著降低TRAP阳性多核细胞与单核-双核细胞的比率，表明对破骨细胞前体融合的影响。目前的数据表明，这个家族的肽不仅作用于成熟的破骨细胞，而且还抑制其在骨髓培养物中的发育。这种活性由胰淀素和CGRP共享。降钙素的效力比胰淀素和CGRP大得多，这与降钙素受体介导的这些肽的作用一致。(C)2001年，Elsevier Science Inc. All rights reserved.
Amylin and calcitonin gene-related peptide (CGRP) are homologous 37 amino acid peptides that are found in the circulation. Both peptides belong to the calcitonin family. Similar to calcitonin, amylin and CGRP inhibit osteoclast activity, although they are much less potent than calcitonin. Calcitonin is known to act on the latter stages of osteoclast development, inhibiting the fusion of committed preosteoclasts to form mature multinucleated cells; however, whether or not calcitonin acts earlier in the formation of the precursor osteoclasts is controversial. The question of osteoclast development has never been examined with respect to amylin and CGRP. These issues are addressed in the present study. We studied the effects of calcitonin (salmon and rat), amylin (human and rat), and CGRP (human and rat) in mouse bone marrow cultures stimulated to generate osteoclasts using 1 alpha ,25-dihydroxyvitamin D-3. Calcitonin dose-dependently decreased the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells as well as TRAP-positive mono-/binucleated cells at concentrations > 10(-13) mol/L. Amylin and CGRP showed similar effects at concentrations > 10(-9) mol/L. In addition, calcitonin substantially reduced the ratio of TRAP-positive multinucleated to mono-binucleated cells, indicating an effect on fusion of osteoclast precursors. The present data establish that this family of peptides not only acts on mature osteoclasts but also inhibits their development in bone marrow cultures. This activity is shared by amylin and CGRP. The much greater potency of calcitonin than amylin and CGRP is consistent with the action of these peptides being mediated by calcitonin receptors. (C) 2001 by Elsevier Science Inc. All rights reserved.