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Sci. Signal., 2 September 2008
Vol. 1, Issue 35, p. ra1
[DOI: 10.1126/scisignal.1159945]
RESEARCH ARTICLES
Editor's Summary
Bone Censor
The extracellular calcium-sensing receptor (CaSR) is a guanine nucleotide-binding protein (G protein)–coupled receptor (GPCR) that responds to changes in the concentration of extracellular calcium ([Ca2+]e) and modulates various functions of parathyroid cells (PTCs), chondrocytes (the cells that produce cartilage), osteoblasts, and renal tubular cells. Previous attempts to characterize the CaSR in Casr–/– mice have been hampered by the expression of an alternatively spliced form of the receptor that provides at least partial compensation for loss of the full-length receptor (see the Perspective by Brown and Lian). Chang et al. have now developed mice with cell type–specific knockout of Casr that do not express the alternative receptor. Mice with PTC- or osteoblast-specific deletion of Casr were viable but had postnatal skeletal defects. Unexpectedly, knockout of Casr in chondrocytes was lethal. Mice in which chondrocyte-specific knockout of Casr was induced late in embryonic life were viable but had delayed growth plate development. Together, these findings reveal a previously unappreciated role for the CaSR in embryonic and postnatal skeletal development.
Citation: W. Chang, C. Tu, T.-H. Chen, D. Bikle, D. Shoback, The Extracellular Calcium-Sensing Receptor (CaSR) Is a Critical Modulator of Skeletal Development. Sci. Signal.1, ra1 (2008).
Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo.
S. J. Quinn, A. R. B. Thomsen, J. L. Pang, L. Kantham, H. Brauner-Osborne, M. Pollak, D. Goltzman, and E. M. Brown (2013)
Am J Physiol Endocrinol Metab
304, E310-E320
|Abstract »|Full Text »|PDF »
Gastric Acid, Calcium Absorption, and Their Impact on Bone Health.
Strontium Is a Biased Agonist of the Calcium-Sensing Receptor in Rat Medullary Thyroid Carcinoma 6-23 Cells.
A. R. B. Thomsen, J. Worm, S. E. Jacobsen, M. Stahlhut, M. Latta, and H. Brauner-Osborne (2012)
J. Pharmacol. Exp. Ther.
343, 638-649
|Abstract »|Full Text »|PDF »
Parathyroid Hormone-Independent Role for the Calcium-Sensing Receptor in the Control of Urinary Calcium Excretion.
D. Riccardi (2012)
J. Am. Soc. Nephrol.
23, 1766-1768
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Chronic Inhibition of ERK1/2 Signaling Improves Disordered Bone and Mineral Metabolism in Hypophosphatemic (Hyp) Mice.
M. Y. H. Zhang, D. Ranch, R. C. Pereira, H. J. Armbrecht, A. A. Portale, and F. Perwad (2012)
Endocrinology
153, 1806-1816
|Abstract »|Full Text »|PDF »
The calcium-sensing receptor complements parathyroid hormone-induced bone turnover in discrete skeletal compartments in mice.
Y. Xue, Y. Xiao, J. Liu, A. C. Karaplis, M. R. Pollak, E. M. Brown, D. Miao, and D. Goltzman (2012)
Am J Physiol Endocrinol Metab
302, E841-E851
|Abstract »|Full Text »|PDF »
Positive and Negative Allosteric Modulators Promote Biased Signaling at the Calcium-Sensing Receptor.
A. E. Davey, K. Leach, C. Valant, A. D. Conigrave, P. M. Sexton, and A. Christopoulos (2012)
Endocrinology
153, 1232-1241
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Successful Use of Bisphosphonate and Calcimimetic in Neonatal Severe Primary Hyperparathyroidism.
A. Wilhelm-Bals, P. Parvex, C. Magdelaine, and E. Girardin (2012)
Pediatrics
129, e812-e816
|Abstract »|Full Text »|PDF »
Negative Cross-talk between Calcium-sensing Receptor and {beta}-Catenin Signaling Systems in Colonic Epithelium.
O. Rey, W. Chang, D. Bikle, N. Rozengurt, S. H. Young, and E. Rozengurt (2012)
J. Biol. Chem.
287, 1158-1167
|Abstract »|Full Text »|PDF »
Mouse models for inherited endocrine and metabolic disorders.
1,25-Dihydroxyvitamin D3 contributes to regulating mammary calcium transport and modulates neonatal skeletal growth and turnover cooperatively with calcium.
J. Ji, R. Lu, X. Zhou, Y. Xue, C. Shi, D. Goltzman, and D. Miao (2011)
Am J Physiol Endocrinol Metab
301, E889-E900
|Abstract »|Full Text »|PDF »
Strontium Ranelate Decreases Receptor Activator of Nuclear Factor-{kappa}B Ligand-Induced Osteoclastic Differentiation In Vitro: Involvement of the Calcium-Sensing Receptor.
A. Caudrillier, A.-S. Hurtel-Lemaire, A. Wattel, F. Cournarie, C. Godin, L. Petit, J.-P. Petit, E. Terwilliger, S. Kamel, E. M. Brown, et al. (2010)
Mol. Pharmacol.
78, 569-576
|Abstract »|Full Text »|PDF »
Comparison of Active Vitamin D Compounds and a Calcimimetic in Mineral Homeostasis.
L. Nguyen-Yamamoto, I. Bolivar, S. A. Strugnell, and D. Goltzman (2010)
J. Am. Soc. Nephrol.
21, 1713-1723
|Abstract »|Full Text »|PDF »
Alterations in phosphorus, calcium and PTHrP contribute to defects in dental and dental alveolar bone formation in calcium-sensing receptor-deficient mice.
W. Sun, W. Sun, J. Liu, X. Zhou, Y. Xiao, A. Karaplis, M. R. Pollak, E. Brown, D. Goltzman, and D. Miao (2010)
Development
137, 985-992
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Physiology and pathophysiology of the calcium-sensing receptor in the kidney.
D. Riccardi and E. M. Brown (2010)
Am J Physiol Renal Physiol
298, F485-F499
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Multiple endocrine neoplasia type 1 knockout mice develop parathyroid, pancreatic, pituitary and adrenal tumours with hypercalcaemia, hypophosphataemia and hypercorticosteronaemia.
B. Harding, M. C Lemos, A. A C Reed, G. V Walls, J. Jeyabalan, M. R Bowl, H. Tateossian, N. Sullivan, T. Hough, W. D Fraser, et al. (2009)
Endocr. Relat. Cancer
16, 1313-1327
|Abstract »|Full Text »|PDF »
Agonists and Allosteric Modulators of the Calcium-Sensing Receptor and Their Therapeutic Applications.
Z. Saidak, M. Brazier, S. Kamel, and R. Mentaverri (2009)
Mol. Pharmacol.
76, 1131-1144
|Abstract »|Full Text »|PDF »
The calcium-sensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretion.
L. Kantham, S. J. Quinn, O. I. Egbuna, K. Baxi, R. Butters, J. L. Pang, M. R. Pollak, D. Goltzman, and E. M. Brown (2009)
Am J Physiol Endocrinol Metab
297, E915-E923
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The full-length calcium-sensing receptor dampens the calcemic response to 1{alpha},25(OH)2 vitamin D3 in vivo independently of parathyroid hormone.
O. Egbuna, S. Quinn, L. Kantham, R. Butters, J. Pang, M. Pollak, D. Goltzman, and E. Brown (2009)
Am J Physiol Renal Physiol
297, F720-F728
|Abstract »|Full Text »|PDF »
No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions.
P. Wellendorph, L. D. Johansen, A. A Jensen, E. Casanova, M. Gassmann, P. Deprez, P. Clement-Lacroix, B. Bettler, and H. Brauner-Osborne (2009)
J. Mol. Endocrinol.
42, 215-223
|Abstract »|Full Text »|PDF »
New Insights in Bone Biology: Unmasking Skeletal Effects of the Extracellular Calcium-Sensing Receptor.
