Human Synthetic Calcitonin Gene-Related Peptide Inhibits Bone Resorption<i>in Vitro</i>*

D'Souza, S M; MacIntyre, I.; Girgis, S. I.; Mundy, Gregory R.

doi:10.1210/endo-119-1-58

Cited by 93 publications

(39 citation statements)

References 12 publications

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“…Tippins et al (1984) demonstrated that CGRP lowers plasma calcium levels in both rats and rabbits in a dose-related manner, thus resembling calcitonin. Inhibition of bone resorption by CGRP has also been demonstrated in vitro (D'Souza et al, 1986;Roos et al, 1986;Yamamoto et al, 1986;Zaidi et al, 1988Zaidi et al, , 1987b. Moreover, administration of CGRP inhibits bone loss in ovariectomized rats (Valentijn et al, 1997).…”

Section: Cgrp and Bone Cellsmentioning

confidence: 84%

Calcitonin gene‐related peptide (CGRP)‐containing nerve fibers in bone tissue and their involvement in bone remodeling

Irie

Hara-Irie

Ozawa

et al. 2002

Microscopy Res & Technique

120

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Bone remodeling is a process of bone renewal accomplished by osteoclastic bone resorption and osteoblastic bone formation. These two activities are regulated by systemic hormones and by local cytokines and growth factors. Moreover, the nervous system and certain neuropeptides seem to be involved in regulation of bone remodeling. In this paper, we focus on the distribution of CGRP-containing nerve fibers and their dynamics, and discuss the role of these fibers as a possible mechanism for nervous system involvement in regulation of bone remodeling. CGRP-immunoreactive nerve fibers are widely distributed in bone tissue, such as periosteum and bone marrow, and show apparent regional distribution with different densities. They are often associated with blood vessels and show a beaded appearance. The wide distribution of CGRP-immunoreactive nerve fibers in bone tissue and the changes in distribution during bone development and regeneration suggest the involvement of these fibers in bone remodeling. The effect of CGRP on bone remodeling could partly be through its action on blood vessels, thereby regulating local blood flow. Moreover, in vitro biochemical data and the localization of CGRP-immunoreactive nerve fibers in the vicinity of bone cells suggest that they are directly involved in local regulation of bone remodeling by elevating the concentration of CGRP in the microenvironment around bone cells, especially during bone growth or repair.

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Section: Cgrp and Bone Cellsmentioning

confidence: 84%

Calcitonin gene‐related peptide (CGRP)‐containing nerve fibers in bone tissue and their involvement in bone remodeling

Irie

Hara-Irie

Ozawa

et al. 2002

Microscopy Res & Technique

120

View full text Add to dashboard Cite

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“…Using human iliac bone marrow cultures of paraplegic patients, Demulder et al [29] have recently shown an increase of osteoclast-like cell formation below the lesional level which they explained by locally elevated IL-6 production arising from modifications in the bone marrow microenvironment in the paralyzed territories. Neurovascular changes secondary to the modification of the autonomic nervous system [24] with decreased local release of neuropeptides (such as calcitonin gene-related peptide) that inhibit bone resorption could directly contribute to the increased resorption activity after SCI [30].…”

Section: Discussionmentioning

confidence: 99%

Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men

Zehnder

Lüthi

Michel

et al. 2004

Osteoporosis International

252

191

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To study the time course of demineralization and fracture incidence after spinal cord injury (SCI), 100 paraplegic men with complete motor loss were investigated in a cross-sectional study 3 months to 30 years after their traumatic SCI. Fracture history was assessed and verified using patients' files and X-rays. BMD of the lumbar spine (LS), femoral neck (FN), distal forearm (ultradistal part = UDR, 1/3 distal part = 1/3R), distal tibial diaphysis (TDIA), and distal tibial epiphysis (TEPI) was measured using DXA. Stiffness of the calcaneus (QUI.CALC), speed of sound of the tibia (SOS.TIB), and amplitude-dependent SOS across the proximal phalanges (adSOS.PHAL) were measured using QUS. Z-Scores of BMD and quantitative ultrasound (QUS) were plotted against time-since-injury and compared among four groups of paraplegics stratified according to time-since-injury (<1 year, stratum I; 1-9 years, stratum II; 10-19 years, stratum III; 20-29 years, stratum IV). Biochemical markers of bone turnover (deoxypyridinoline/creatinine (D-pyr/Cr), osteocalcin, alkaline phosphatase) and the main parameters of calcium phosphate metabolism were measured. Fifteen out of 98 paraplegics had sustained a total of 39 fragility fractures within 1,010 years of observation. All recorded fractures were fractures of the lower limbs, mean time to first fracture being 8.9 ± 1.4 years. Fracture incidence increased with time-after-SCI, from 1% in the first 12 months to 4.6%/year in paraplegics since >20 years (p<.01). The overall fracture incidence was 2.2%/year. Compared with nonfractured paraplegics, those with a fracture history had been injured for a longer time (p<.01). Furthermore, they had lower Z-scores at FN, TEPI, and TDIA (p<.01 to <.0001), the largest difference being observed at TDIA, compared with the nonfractured. At the lower limbs, BMD decreased with time at all sites (r=.49 to .78, all p<.0001). At FN and TEPI, bone loss followed a log curve which leveled off between 1 to 3 years after injury. In contrast, Z-scores of TDIA continuously decreased even beyond 10 years after injury. LS BMD Z-score increased with time-since-SCI (p<.05). Similarly to DXA, QUS allowed differentiation of early and rapid trabecular bone loss (QUI.CALC) vs slow and continuous cortical bone loss (SOS.TIB). Biochemical markers reflected a disproportion between highly elevated bone resorption and almost normal bone formation early after injury. Turnover declined following a log curve with time-after-SCI, however, D-pyr/Cr remained elevated in 30% of paraplegics injured >10 years. In paraplegic men early (trabecular) and persistent (cortical) bone loss occurs at the lower limbs and leads to an increasing fracture incidence with time-after-SCI.

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“…CGRP-containing fibers have also been shown to contact osteoclasts within the bone microenvironment, suggesting that CGRP may also control osteoclast differentiation or function [91,92]. Supporting this hypothesis, CGRP inhibits bone resorption in vitro [93][94][95][96]. However, no bone resorption abnormalities have been observed in Cgrp -deficient mice [89].…”

Section: More Complexity To Comementioning

confidence: 92%

Regulation of bone remodeling by the central and peripheral nervous system

Elefteriou

2008

Archives of Biochemistry and Biophysics

205

150

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The homeostatic nature of bone remodeling has become a notion further supported lately by the demonstration that neuropeptides and their receptors regulate osteoblast and osteoclast function in vivo. Following initial studies reporting the presence of nerves and nerve-derived products within the bone micro-environment and the expression of receptors for these neuropeptides in bone cells, new experimental and mechanistic evidence based on in vivo murine genetic and pharmacologic models recently demonstrated that inputs from the central and peripheral nervous system feed into the already complex regulatory machinery controlling bone remodeling. The function of a number of "osteo-neuromediators" has been characterized, including norepinephrine and the beta 2-adrenergic receptor, Neuropeptide Y and the Y1 and Y2 receptors, endocannabinoids and the CB1 and CB2 receptors, as well as dopamine, serotonin and their receptors and transporters, Calcitonin gene-related peptide, and neuronal NOS. This new body of evidence suggests that neurons in the central nervous system integrate clues from the internal and external milieux, such as energy homeostasis, glycemia or reproductive signals, with the regulation of bone remodeling. The next major tasks in this new area of bone biology will be to understand, at the molecular level, the mechanisms by which common central neural systems regulate and integrate these major physiological functions, the relative importance of the central and peripheral actions of neuropeptides present in both compartments and their relationship, and how bone cells signal back to central centers, because the definition of a homeostatic function implies the existence of feedback signals. Together, these findings shed a new light on the complexity of the mechanisms regulating bone remodeling and uncovered new potential therapeutic strategies for the design of bone anabolic treatments. This review summarizes the latest advances in this area, focusing on investigations based on in vivo animal studies. KeywordsBone; osteoblast; osteoclast; neuron; sympathetic nervous system; hypothalamus; leptin; neuropeptide; adrenergic receptor; neuropeptide Y; endocannabinoid The central nervous system restrains bone formationIt is the association between body weight and bone density as well as the association between loss of gonadal function and osteoporosis that initially pointed to the putative existence of a common factor regulating body weight, reproduction and bone mass. Based on the knowledge that the adipocyte-derived hormone leptin regulates major physiological functions, including body weight and reproduction, via the hypothalamus and its receptor ObRb, it was

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Human Synthetic Calcitonin Gene-Related Peptide Inhibits Bone Resorptionin Vitro*

Cited by 93 publications

References 12 publications

Calcitonin gene‐related peptide (CGRP)‐containing nerve fibers in bone tissue and their involvement in bone remodeling

Calcitonin gene‐related peptide (CGRP)‐containing nerve fibers in bone tissue and their involvement in bone remodeling

Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men

Regulation of bone remodeling by the central and peripheral nervous system

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