Vol. 284, Issue 6, E1181-E1190, June 2003
-Melanocyte-stimulating hormone is a novel regulator of
bone
Jillian
Cornish1,
Karen E.
Callon1,
Kathleen G.
Mountjoy2,
Usha
Bava1,
Jian-Ming
Lin1,
Damian E.
Myers3,
Dorit
Naot1, and
Ian R.
Reid1
1 Departments of Medicine and
2 Molecular Medicine and Physiology, University of
Auckland, Auckland 1001, New Zealand; and
3 Department of Clinical and Biomedical Sciences,
Barwon Health, University of Melbourne, Melbourne 3220, Australia
-Melanocyte-stimulating hormone
(
-MSH), a 13-amino acid peptide produced in the brain and
pituitary gland, is a regulator of appetite and body weight, and its
production is regulated by leptin, a factor that affects bone mass when
administered centrally.
-MSH acts via melanocortin receptors. Humans
deficient in melanocortin receptor 4 (MC4-R) have increased bone mass,
and MC4-R has been identified in an osteoblast-like cell line. Thus
-MSH may act directly on the skeleton, a question addressed by the
present studies. In primary cultures of osteoblasts and chondrocytes,
-MSH dose dependently (
10
9 M) stimulated cell
proliferation. In bone marrow cultures,
-MSH (>10
9 M)
stimulated osteoclastogenesis. Systemic administration of
-MSH to
mice (20 injections of 4.5 µg/day) decreased the trabecular bone
volume in the proximal tibiae from 19.5 ± 1.8 to 15.2 ± 1.4% (P = 0.03) and reduced trabecular number
(P = 0.001). Radiographic indexes of trabecular bone,
assessed by phase-contrast X-ray imaging, confirmed the bone loss. It
is concluded that
-MSH acts directly on bone, increasing bone
turnover, and, when administered systemically, it decreases bone
volume. The latter result may also be contributed to by
-MSH effects
elsewhere, such as the adipocyte, pancreatic
-cell, or central
nervous system.
osteoblast; osteoclast; chondrocyte; systemic administration