共 19 条
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.
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页码:240 / 246
页数:7
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