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

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• 作者：Cornish ; Jillian ; Grey ; Andrew ; Callon ; Karen E. ; Naot ; Dorit ; Hill ; Bernadine L. ; Lin ; Cindy Q.X. ; et. al.
• 关键词：Osteoblast ; Calcitonin-like ; In vitro ; MAP-kinase ; IGF-1 receptor
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：May 21, 2004
• 年：2004
• 卷：318
• 期：1
• 页码：240-246
• 全文大小：335 K

文摘

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 osteoblastic 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.