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 inhibits osteoclasts, stimulates insulin-like growth factor I and inhibits tumor necrosis factor alpha production by osteoblasts in vitro. To investigate 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 osteocalcin promoter (Ost-CGRP tg+ mice). Calvaria cultures from transgene positive (tg+), but not tg- mice, produced bioactive CGRP. Trabecular bone density and bone volume, determined by peripheral quantitative computed tomography 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 result of ovariectomy, but remained higher than in sham tg- mice. Targeting CGRP to osteoblasts appears to favor the establishment of a higher trabecular bone mass in mice.
Yale University School of Medicine, Department of Orthopaedics and Rehabilitation, New Haven, Connecticut 06510, USA.
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Ballica
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Valentijn
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Khachatryan
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Guerder
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Kapadia
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Gundberg
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Gilligan
R A
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Flavell
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Vignery
D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000378:metabolism; D046508:Culture Techniques; D004967:Estrogens / Q000172:deficiency; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000378:metabolism; D014057:Tomography, X-Ray Computed
D017077:Culture Media, Conditioned; D004967:Estrogens; D015675:Osteocalcin; D015740:Calcitonin Gene-Related Peptide