Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
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).
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.