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Sci. Signal., 2 September 2008
Vol. 1, Issue 35, p. ra1
[DOI: 10.1126/scisignal.1159945]
RESEARCH ARTICLES
The Extracellular Calcium-Sensing Receptor (CaSR) Is a Critical Modulator of Skeletal Development
Wenhan Chang*,
Chialing Tu*,
Tsui-Hua Chen,
Daniel Bikle, and
Dolores Shoback
Endocrine Research Unit, Department of Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco, CA 94121, USA.
* These authors contributed equally to this work.
Abstract:
The extracellular Ca2+-sensing receptor (CaSR) plays a nonredundant role in the functions of the parathyroid gland (PTG) and the kidney. Severe hyperparathyroidism, premature death, and incomplete gene excision in Casr–/– mice have precluded the assessment of CaSR function in other tissues. We generated mice with tissue-specific deletion of Casr in the PTG, bone, or cartilage. Deletion of Casr in the PTG or bone resulted in profound bone defects, whereas deletion of Casr in chondrocytes (cartilage-producing cells) resulted in death before embryonic day 13 (E13). Mice in which chondrocyte-specific deletion of Casr was induced between E16 and E18 were viable but showed delayed growth plate development. Our data show a critical role for the CaSR in early embryogenesis and skeletal development.
To whom correspondence should be addressed. E-mail: wenhan.chang{at}ucsf.edu
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
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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.