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

Hoff, Ana O.; Catalá-Lehnen, Philip; Thomas, Peedikayil E.; Priemel, Matthias; Rueger, Johannes M.; Nasonkin, Igor O.; Bradley, Allan; Hughes, Mark; Ordóñez, Nelson G.; Cote, Gilbert J.; Amling, Michael; Gagel, Robert F.

doi:10.1172/jci14218

Cited by 69 publications

(94 citation statements)

References 57 publications

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“…On the other hand, there is a rapid accommodation to calcitonin, and response of osteoclasts is attenuated within a day. Further, in mouse models, deletion of calcitonin [39] or its receptor [20], do not reduce bone mass as expected.…”

Section: Regulation Of Osteoclasts By Systemic Hormonessupporting

confidence: 56%

Osteoclastic differentiation and function regulated by old and new pathways

Blair

Zaidi

2006

Rev Endocr Metab Disord

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The osteoclast is a specialized multinucleated variant of the macrophage family. It degrades mineralized tissue, and is required for modeling and remodeling of bone. The osteoclast has long been known to require vitamin D for its differentiation and to be regulated by parathyroid hormone via circulating Ca(2+) levels. Two local signals important in osteoclast survival and differentiation, CSF-1 and RANKL, were characterized by the mid-1990 s. A basic framework of specialized cell attachment and resorption molecules was also clear by that time, including the alpha(v)beta(3) integrin, the key adhesion molecule of the mature osteoclast, the highly expressed vacuolar-type H(+)-ATPase that drives acid secretion to dissolve mineral, and cathepsin K, the predominant acid proteinase for collagenolysis. Recently, additional detail has been added to this framework, showing that the osteoclast has more complex regulation than was previously believed. These include the findings that one component of the V-H(+)-ATPase is unique to the osteoclast, that chloride transport and probably Cl(-)/H(+) exchange are also required for mineral degradation, and that additional receptors besides RANK and Fms regulate osteoclast formation and survival. Additional receptors include estrogen receptor-alpha, TNF-family receptors other than RANK, and, at least in some cases, glycoprotein hormone receptors including the TSH-R and the FSH-R. Challenges in understanding osteoclast biology include how the signalling mechanisms function cooperatively. Recent findings suggest that there is a network of cytoplasmic adapters, including Gab-2 and BCAR1, which are modified by multiple signalling mechanisms and which serve to integrate the signalling pathways.

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Section: Regulation Of Osteoclasts By Systemic Hormonessupporting

confidence: 56%

Osteoclastic differentiation and function regulated by old and new pathways

Blair

Zaidi

2006

Rev Endocr Metab Disord

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“…As regard to the inhibitory action of calcitonin on bone resorption, it would be legitimate to hypothesize that bone resorption should be the primary target of calcitonin increase. However, recent evidence made with genetic ablation of either the calcitonin or calcitonin receptor genes highlighted an unexpected phenotype of high bone mass with no or little apparent effect on bone resorption (Hoff et al 2002, Dacquin et al 2004, Davey et al 2008. This unexpected phenotype indicated a possible inhibitory action (direct or indirect) of calcitonin on bone formation without affecting bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor

Mabilleau¹,

Mieczkowska²,

Irwin³

et al. 2013

Journal of Endocrinology

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Bone is permanently remodeled by a complex network of local, hormonal, and neuronal factors that affect osteoclast and osteoblast biology. Among these factors, a role for gastrointestinal hormones has been proposed based on the evidence that bone resorption dramatically falls after a meal. Glucagon-like peptide-1 (GLP1) is one of these gut hormones, and despite several reports suggesting an anabolic effect of GLP1, or its stable analogs, on bone mass, little is known about the effects of GLP1/GLP1 receptor on bone strength. In this study, we investigated by three-point bending, quantitative X-ray microradiography, microcomputed tomography, qBEI, and FTIRI bone strength and bone quality in male Glp1r knockout (Glp1r KO) mice when compared with control WT animals. Animals with a deletion of Glp1r presented with a significant reduction in ultimate load, yield load, stiffness, and total absorbed and post-yield energies when compared with WT animals. Furthermore, cortical thickness and bone outer diameter were significantly decreased in deficient animals. The mineral quantity and quality were not significantly different between Glp1r KO and WT animals. On the other hand, the maturity of the collagen matrix was significantly reduced in deficient animals and associated with lowered material properties. Taken together, these data support a positive effect of GLP1R on bone strength and quality. Key Words" bone quality " glucagon-like peptide-1 " bone strength " bone matrix " bone mineral

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“…Amylin and CGRP are co-expressed by primary sensory neurons and their peripheral axons (Mulder et al 1995). In addition, these peptides have been considered to have similar functions to bone remodeling (Hoff et al 2002). Like CGRP, amylin can increase osteoblast proliferation and decrease osteoclast activity.…”

Section: Discussionmentioning

confidence: 99%

Increase of CGRP-Containing Nerve Fibers in the Rat Periodontal Ligament After Luxation

et al. 2011

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The distribution of calcitonin gene-related peptide (CGRP) was examined in the periodontal ligament (PDL) after experimental luxation injury of the rat first molar tooth. The luxational injury increased the number of CGRP-immunoreactive (IR) nerve fibers. At 3-7 days, numerous CGRP-IR nerve fibers appeared throughout the injured PDL. These nerve fibers terminated as free nerve endings within resorption cavities. Immunohistochemistry for receptor activity modifying protein 1 (RAMP1) also demonstrated that the subunit of CGRP receptor was expressed by periodontal cells adjacent to the alveolar bone in the intact and injured PDL. RAMP1-IR cells were divided into two types; small cells with single nucleus and large cells with 2-6 nuclei. After the luxational injury, both types of RAMP1-IR cells abundantly appeared within resorption cavities. As a result, the treatment increased the number of large RAMP1-IR cells at 3-7 days and small RAMP1-IR cells at 7 days. In addition, a double immunofluorescence analysis demonstrated that CGRP-IR nerve fibers were seen away from RAMP1-IR cells in the intact PDL. After the traumatic injury, however, CGRP-IR nerve fibers appeared in the close vicinity of small and large RAMP1-IR cells at 5-7 days. The morphology and distribution of RAMP1-IR cells suggest that they contain osteoblasts and osteoclasts. By affecting osteoclasts and osteoblasts, CGRP may have effects on bone remodeling in the luxated PDL.

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

Cited by 69 publications

References 57 publications

Osteoclastic differentiation and function regulated by old and new pathways

Osteoclastic differentiation and function regulated by old and new pathways

Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor

Increase of CGRP-Containing Nerve Fibers in the Rat Periodontal Ligament After Luxation

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