Systemic administration of adrenomedullin(27-52) increases bone volume and strength in male mice

Abstract

Adrenomedullin is a 52-amino acid peptide first described in a human phaeochromocytoma but since been found to be present in many tissues, including the vascular system and bone. Because of its structural similarity to amylin and calcitonin gene-related peptide, both of which have actions on bone cells, we have previously assessed the effects of adrenomedullin on the skeleton, and found that it increases osteoblast proliferation in vitro and bone formation following local injection in vivo. The present study carries this work forward by assessing the effects on bone of the systemic administration of a fragment of this peptide lacking the structural requirements for vasodilator activity. Two groups of 20 adult male mice received 20 injections of human adrenomedullin(27-52) 8·1 µg or vehicle over a 4-week period and bone histomorphometry and strength were assessed.In the tibia, adrenomedullin(27-52) produced increases in the indices of osteoblast activity, osteoid perimeter and osteoblast perimeter (P<0·05 for both using Student's t-test). Osteoclast perimeter was not affected. There was a 21% increase in cortical width and a 45% increase in trabecular bone volume in animals treated with adrenomedullin(27-52) (P<0·002 for both). Assessment of bone strength by three-point bending of the humerus showed both the maximal force and the displacement to the point of failure were increased in the animals treated with adrenomedullin(27-52) (P<0·03 for both). There was also a significant increase in the thickness of the epiphyseal growth plate. No adverse effects of the treatment were noted.It is concluded that adrenomedullin(27-52) acts as an anabolic agent on bone. These findings may be relevant to the normal regulation of bone mass and to the design of agents for the treatment of osteoporosis.

α-Melanocyte-stimulating hormone is a novel regulator of bone

“…In the case of chondrocytes, this is reflected in the lack of effect of ␣-MSH on the width of the growth plate or on tibial growth. This contrasts with our previous work in this mouse model, in which factors stimulating chondrocyte proliferation to a degree comparable to that seen with ␣-MSH have also increased growth plate width and tibial length in vivo (7,12). It is likely that the catabolic effects of systemically administered ␣-MSH mediated by the hormonal and neuronal mechanisms discussed in the three preceding paragraphs also account for this dissociation of its in vitro and in vivo effects on cartilage.…”

“…Two groups of 20 sexually mature male Swiss mice, aged between 40 and 50 days and weighing 25-36 g, were given daily subcutaneous injections (4.5 g of ␣-MSH in 50 l of water or water alone) in the loose skin at the nape of the neck for 5 days/wk over 4 consecutive weeks. This dose was chosen because the same molar doses of amylin and adrenomedullin in this model produce substantial effects on bone turnover and bone area (7,12), and these peptides have similar effects on osteoblast proliferation. Animals were housed in a room maintained at 20°C on a 12:12-h light-dark cycle.…”

Detection of significant pathways in osteoporosis based on graph clustering

“…ADM is a 52-amino acid peptide first described in a human phaeochromocytoma but has since been identified in numerous tissues, including the bone (44). Systemic administration of ADM stimulates the proliferation of osteoblasts and promotes bone growth (45).…”

Current, new and future treatments of osteoporosis

“…Their anabolic effects on bone are predominant when used systemically [131][132][133][134][135]. Their co-expression on osteoblasts especially during embryogenesis more intensifies their role as a local regulator of bone growth [136,137].…”