Journal
BONE
Volume 46, Issue 3, Pages 571-576Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2009.07.082
Keywords
Calcium-sensing receptor; Bone cells; Osteoporosis; Strontium
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Recent progress has been made in our understanding of the functional role of the seven-transmembrane-spanning extracellular calcium-sensing receptor (CaSR) in bone cells. Both in vitro and in vivo data indicate that the CaSR is a physiological regulator of bone cell metabolism. The CaSR regulates the recruitment, differentiation and survival of osteoblasts and osteoclasts through activation of multiple CaSR-mediated intracellular signaling pathways in bone cells. This raises the possibility that the bone CaSR could potentially be targeted by allosteric modulators, either agonists (calcimimetics) or antagonists (calcilytics) to control bone remodeling. The therapeutic potential of CaSR agonists or antagonists in bone cells is however hampered by their effects on the CaSR in nonskeletal tissues. Rather, direct targeting of the bone CaSR may be of potential interest for the treatment of bone diseases. Targeting the bone CaSR using a bone-seeking CaSR agonist offers a potential mean to modulate bone cell metabolism. The development Of drugs that preferentially tat-get the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis. (C) 2009 Elsevier Inc. All rights reserved.
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