Skeletal Effects of Amylin and Related Peptides

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Abstract

Amylin and adrenomedullin are related peptides with some homology to both calcitonin and calcitonin gene-related peptide. Both amylin and adrenomedullin recently have been found to stimulate the proliferation of osteoblasts in vitro and to increase indices of bone formation when administered either locally or systemically in vivo. Amylin also has been found to act on chondrocytes, stimulating their proliferation in culture and increasing tibial growth plate width and tibial length when administered systemically to adult mice. Systemic administration of amylin also is associated with increased fat mass, consistent with its known effects on fuel metabolism. However, we recently have established that the osteotropic effects of amylin are retained in an octapeptide fragment of the molecule, which has no activity on carbohydrate metabolism. Thus, this small peptide, or analogues of it, are potential candidates as anabolic therapies for osteoporosis. Similar fragments of adrenomedullin, which retain activity on bone but lack the parent peptide's vasodilator properties, also are being denned. In addition to a potential therapeutic role, these peptides may play a part in normal bone physiology. Amylin is secreted after eating and may direct calcium and protein absorbed from the meal into new bone synthesis. Amylin circulates in high concentrations in obese individuals and might contribute to the association between bone mass and fat mass. Finally, adrenomedullin and its receptor are easily detectable during rodent embryogenesis, suggesting that these peptides also might act as autocrine or paracrine regulators of bone growth. Further research is necessary to confirm these interesting possibilities.

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