Evaluation of the<i>in Vivo</i>and<i>in Vitro</i>Calcium Regulating Actions of Noncalcitonin Peptides Produced via Calcitonin Gene Expression*

Roos, Bernard A.; Fischer, Jan A.; Pignat, Werner; Alander, Cynthia B.; Raisz, Lawrence G.

doi:10.1210/endo-118-1-46

Cited by 107 publications

(59 citation statements)

References 33 publications

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“…Rat CT but not rat CGRP, at doses between 10 and 100 pg/g (2.94 × 10 -15 to 2.94 × 10 -14 mol/g) body weight, inhibited the PTH-mediated rise in serum calcium concentration (Figure 2c). The half-maximal effect of approximately 30 pg/g body weight is nearly identical to that described for the effect of CT to lower the serum calcium concentration under basal conditions in two prior reports (38,39). Effects of CGRP were observed only at higher concentrations, similar to previously reported results (Figure 2d) (38,39).…”

supporting

confidence: 89%

Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene

Hoff¹,

Catalá-Lehnen²,

Thomas³

et al. 2002

J. Clin. Invest.

189

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Calcitonin (CT) is a known inhibitor of bone resorption. Calcitonin gene–related peptide-α (CGRPα), produced by alternative RNA processing of the CT/CGRP gene, has no clearly defined role in bone. To better understand the physiologic role of the CT/CGRP gene we created a mouse in which the coding sequences for both CT and CGRPα were deleted by homologous recombination. The CT/CGRP–/– knockout (KO) mice procreated normally, there were no identifiable developmental defects at birth, and they had normal baseline calcium-related chemistry values. However, KO animals were more responsive to exogenous human parathyroid hormone as evidenced by a greater increase of the serum calcium concentration and urine deoxypyridinoline crosslinks, an effect reversed by CT and mediated by a greater increase in bone resorption than in controls. Surprisingly, KO mice have significantly greater trabecular bone volume and a 1.5- to 2-fold increase in bone formation at 1 and 3 months of age. This effect appears to be mediated by increased bone formation. In addition, KO mice maintain bone mass following ovariectomy, whereas wild-type mice lose approximately one-third of their bone mass over 2 months. These findings argue for dual roles for CT/CGRP gene products: prevention of bone resorption in hypercalcemic states and a regulatory role in bone formation

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supporting

confidence: 89%

Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene

Hoff¹,

Catalá-Lehnen²,

Thomas³

et al. 2002

J. Clin. Invest.

189

View full text Add to dashboard Cite

show abstract

“…Recently, neuronal factors, in particular, neuropeptides, have been reported to regulate bone cells (Konttinen et al 1996). CGRP has been reported to recruit macrophages into osteoclast-like cells (Owan and Ibaraki 1994), to inhibit bone resorption (Roos et al 1986), and to stimulate osteogenesis (Bernard and Shih 1990). It is possible that the allelic genotype associated with the lower BMD in our test subjects may be in linkage disequilibrium with a mutation in CGRP; another possibility is involvement of the gene encoding PTH, which lies in the same genomic vicinity as CT (Kittur et al 1985).…”

Section: Discussionmentioning

confidence: 99%

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus

et al. 2000

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Calcitonin (CT), a calcium-regulating hormone, lowers the calcium level in serum by inhibiting bone resorption. Because CT may play a role in the pathogenesis of osteoporosis, genetic variations in or adjacent to the CT gene may be associated with variations in bone mineral density (BMD). The present study examined the correlation between a dinucleotide (cytosine-adenine; CA) repeat polymorphism at the CT locus and BMD in 311 Japanese postmenopausal women (mean age, 64.1 years). Seven alleles were present in this population; each allele contained 10, 11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated the respective genotypes A10, A11, A16, A17, A18, A19, and A20. The A10 and A17 alleles were the predominant alleles in the population studied. Z scores (a parameter representing deviation from the age-specific weight-adjusted average BMD) were compared between individuals that possessed one or two alleles of each genotype and those that did not possess the allele. Subjects who possessed one or two A10 alleles had lower BMD Z scores than those who did not (lumbar 2-4 BMD Z score; Ϫ0.148 Ϯ 1.23 vs 0.182 Ϯ 1.54; P ϭ 0.04). No significant relationships were observed between allelic status and background data or biochemical parameters. The significant association observed between BMD and genetic variations at the CT locus implies that polymorphism at this locus may be a useful marker for the genetic study of osteoporosis.

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“…VIP, CGRP, and bradykinin can influence bone resorptive processes (Hohman et al 1983, Gustafson and Lerner 1984, D'Souza et al 1986, Roos et al 1986, Zaidi et al 1987. Since the neuropeptides are most abundant in areas with high mineral turnover and in connection to blood vessel walls (Bjurholm 1989), the peptides may play an integrating role in bone physiology.…”

Section: Discussionmentioning

confidence: 99%

Vasorelaxation in isolated bone arteries: Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide bradykinin studied in pigs

Lundgaard¹,

Aalkjær²,

Bjurholm

et al. 1997

Acta Orthopaedica Scandinavica

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Evaluation of thein Vivoandin VitroCalcium Regulating Actions of Noncalcitonin Peptides Produced via Calcitonin Gene Expression*

Cited by 107 publications

References 33 publications

Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene

Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus

Vasorelaxation in isolated bone arteries: Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide bradykinin studied in pigs

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