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Cornish, J. et al.

Cornish, Grey, Callon, Naot, Hill, Lin, Balchin, Reid,

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

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.[1]

References

Shared pathways of osteoblast mitogenesis induced by amylin, adrenomedullin, and IGF-1. Cornish, J., Grey, A., Callon, K.E., Naot, D., Hill, B.L., Lin, C.Q., Balchin, L.M., Reid, I.R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]

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