Shared pathways of osteoblast mitogenesis induced by amylin, adrenomedullin, and IGF-1

被引:40
作者
Cornish, J [1 ]
Grey, A [1 ]
Callon, KE [1 ]
Naot, D [1 ]
Hill, BL [1 ]
Lin, CQX [1 ]
Balchin, LM [1 ]
Reid, IR [1 ]
机构
[1] Univ Auckland, Dept Med, Auckland, New Zealand
关键词
osteoblast; calcitonin-like; in vitro; MAP-kinase; IGF-1; receptor;
D O I
10.1016/j.bbrc.2004.04.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Amylin and adrenomedullin, members of the calcitonin peptide family, are anabolic to bone. Here, we report overlapping molecular mechanisms by which amylin, adrenomedullin, and IGF-1 induce osteoblast proliferation. Co-treatment of ostcoblastic cells with amylin or adrenomedullin and IGF-1 failed to induce an additive mitogenic effect. In osteoblastic cells, neutralization of the IGF-1 receptor blocked the proliferative effects of amylin and adrenomedullin, while neutralization of IGF-1 did not. Neither amylin- nor adrenomedullin-induced mitogenic signaling or cell proliferation in IGF-1 receptor-null fibroblasts. In addition, amylin and adrenomedullin receptor blockers inhibited the proliferative effects of IGF-1 in osteoblastic cells. These findings demonstrate overlap in the molecular mechanisms by which amylin, adrenomedullin, and IGF-1 induce mitogenesis in osteoblasts, and an important role for the IGF-1 receptor in the mitogenic actions of amylin and adrenomedullin. Our findings are potentially important in refining these peptides for the therapy of osteoporosis. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:240 / 246
页数:7
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