Systemic administration of adrenomedullin(27-52) increases bone volume and strength in male mice
Open accessAbstract
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 microg 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.
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Despite adrenomedullin receptors on osteoclasts and its ability to induce cAMP, adrenomedullin does not affect osteoclast differentiation or activity.
“Despite the presence of adrenomedullin receptors on osteoclasts and the ability of adrenomedullin to induce the synthesis of cAMP in these cells, studies have consistently shown that adrenomedullin does not affect the differentiation and activity of osteoclasts.”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [43]
The Discussion (page unavailable) says this study found no statistically significant increase in bone resorption, although osteoclast perimeter trended upward. It also reports that an earlier study found a significant increase in bone resorption after local adrenomedullin injection, contrary to the claim that studies consistently show no effect on osteoclast activity. The paper does not establish the claimed receptors, cAMP response, or lack of effect on osteoclast differentiation. (LLM, conf=0.85)
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- Authors
- Cornish, J., Callon, K., Bava, U., Coy, D., Mulvey, T., Murray, M., Cooper, G., Cooper, G., & Reid, I.
- Affiliations
- University of Auckland (NZ)
- Tulane University (US)
- Corresponding author
- Cornish, J
- ORCID
- Cornish, J
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2001-07-01
- Volume
- 170
- Issue
- 1
- Pages
- 251-257
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2155995762
- Semantic Scholar
- 9752de6f99f8f80d1006617f546eb0c351b6e030
- Cited by
- 37
- References
- 18
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Auckland Medical Research Foundation
- Health Research Council of New Zealand
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- adrenomedullin, bone formation, bone volume, bone strength, trabecular bone, cortical bone, osteoblast activity, growth plate, osteoporosis treatment, bone histomorphometry, three-point bending
- MeSH terms
- Animals, Biomechanical Phenomena, Body Composition, Bone and Bones, Humerus, Male, Osteoblasts, Peptide Fragments, Tibia, Statistics, Nonparametric, Mice, Adrenomedullin
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