Targeted expression of calcitonin gene-related peptide to osteoblasts increases bone density in mice

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.