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2015 ; 277
(6
): 681-9
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Bone and the regulation of global energy balance
#MMPMID25597336
Zhang Q
; Riddle RC
; Clemens TL
J Intern Med
2015[Jun]; 277
(6
): 681-9
PMID25597336
show ga
The skeleton, populated by large numbers of osteoblasts and long-lived
osteocytes, requires a constant supply of energy-rich molecules to fuel the
synthesis, deposition and mineralization of bone matrix during bone modelling and
remodelling. When these energetic demands are not met, bone acquisition is
suppressed. Recent findings suggest that key developmental signals emanating from
Wnt low-density lipoprotein-related receptor 5 and hypoxia-inducible factor
pathways impact osteoblast bioenergetics to accommodate the energy requirements
for bone cells to fulfil their function. In vivo studies in several mutant mouse
strains have confirmed a link between bone cells and global metabolism,
ultimately leading to the identification of hormonal interactions between the
skeleton and other tissues. The hormones insulin and leptin affect postnatal bone
acquisition, whilst osteocalcin produced by the osteoblast in turn stimulates
insulin secretion by the pancreas. These observations have prompted additional
questions regarding the nature of the mechanisms of fuel sensing and processing
in the osteoblast and their contribution to overall energy utilization and
homeostasis. Answers to such questions should advance our understanding of
metabolic diseases and may ultimately improve management of affected patients. In
this review, we highlight recent studies in this field and offer a perspective on
the evolutionary implications of bone as a metabolic endocrine organ.
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