R. Ballica et al., Targeted expression of calcitonin gene-related peptide to osteoblasts increases bone density in mice, J BONE MIN, 14(7), 1999, pp. 1067-1074
The neuropeptide calcitonin gene-related peptide (CGRP) is concentrated in
fine sensory nerve endings innervating all tissues, including bone, CGRP in
hibits osteoclasts, stimulates insulin-like growth factor I and inhibits tu
mor necrosis factor alpha production by osteoblasts in vitro. To investigat
e the role of CGRP in bone in vivo, mice were engineered to express CGRP in
osteoblasts by placing the human CGRP gene under the control of the rat os
teocalcin promoter (Ost-CGRP tg+ mice), Calvaria cultures from transgene po
sitive (tg+), but not tg- mice, produced bioactive CORP, Trabecular bone de
nsity and bone volume, determined by peripheral quantitative computed tomog
raphy and bone histomorphometry, respectively, were higher in tg+ than tg-
littermates. This increase in bone volume was associated with an increased
bone formation rate. Trabecular bone density decreased in tg+ mice as a res
ult of ovariectomy, but remained higher than in sham tg- mice. Targeting CG
RP to osteoblasts appears to favor the establishment of a higher trabecular
bone mass in mice.