Increased bone mass in a calcitonin knockout mouse full of surprises
Bone is in a constant state of remodeling, during which osteoclasts remove old bone (resorption) and osteoblasts form new bone (formation). Calcitonin is a hormone produced by the thyroid gland and inhibits bone resorption. Following menopause, the rate of bone loss is accelerated, however women with post-menopausal osteoporosis that are treated with calcitonin (by injection or nasal spray) demonstrate increased bone mass and strength, in addition to a decrease in the rate of bone fractures. Following alternative processing, the gene encoding calcitonin (CT/CGRP) also encodes a second peptide: calcitonin gene-related peptide-a (CGRPa), however the role of this peptide in bone metabolism has not been clearly defined.
To better understand the role of calcitonin and CGRP-a in bone metabolism Robert Gagel and colleagues at the University of Texas M.D. Anderson Cancer Center, USA, created mice in which the CT/CGRP gene had been deleted. Given that both calcitonin and CGRP have been shown to inhibit bone resorption and CGRP is known to stimulate bone formation, the authors predicted that there would be either no effect of this deletion on bone mass, or there could be some bone loss.
In the December 16 issue of the Journal of Clinical Investigation, the
authors report their surprising finding that CT/CGRP-deficient mice have
greater bone mass, increased bone formation, and were able to maintain bone
mass during estrogen deficiency by increasing bone formation. These findings
suggest an important and novel function for the products of the CT/CGRP
gene, that was previously unrecognized. They also suggest that the
development of an antagonist to the CT/CGRP gene product(s) may be useful in
the prevention of bone loss associated wi
Contact: Brooke Grindlinger, Ph.D.
Journal of Clinical Investigation