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Sci. Signal., 2 September 2008
Vol. 1, Issue 35, p. pe40
[DOI: 10.1126/scisignal.135pe40]


New Insights in Bone Biology: Unmasking Skeletal Effects of the Extracellular Calcium–Sensing Receptor

Edward M. Brown1 and Jane B. Lian2*

1 Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 20115, USA.
2 Department of Cell Biology and Orthopedic Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Abstract: Experiments performed in mice in which expression of the extracellular calcium–sensing receptor (CaSR) was completely nullified specifically in parathyroid cells, chondrocytes, or cells of the osteoblast lineage have identified phenotypes that indicate a key role for the CaSR in embryonic development of the skeleton, postnatal bone formation, and osteoblast differentiation that are independent of the calcitropic hormone axis. These long-awaited studies further clarify the signaling relationships between the parathyroid gland, kidney, and metabolic bone disease in patients with mutations in the gene encoding the CaSR, and they provide new insights into understanding the signaling pathways involving the CaSR in skeletal cells.

* Corresponding author. E-mail, jane.lian{at}

Citation: E. M. Brown, J. B. Lian, New Insights in Bone Biology: Unmasking Skeletal Effects of the Extracellular Calcium–Sensing Receptor. Sci. Signal. 1, pe40 (2008).

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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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