The calcium-sensing receptor in bone cells: A potential therapeutic target in osteoporosis
Abstract 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 reg...
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| Veröffentlicht in: | Bone (New York, N.Y.) N.Y.), 2010-03, Vol.46 (3), p.571-576 |
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| description | Abstract 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 target the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis. |
| doi_str_mv | 10.1016/j.bone.2009.07.082 |
| format | Article |
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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 target the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis.</description><identifier>ISSN: 8756-3282</identifier><identifier>EISSN: 1873-2763</identifier><identifier>DOI: 10.1016/j.bone.2009.07.082</identifier><identifier>PMID: 19660583</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Bone cells ; Calcium-sensing receptor ; Diseases of the osteoarticular system ; Drug Delivery Systems - methods ; Fundamental and applied biological sciences. Psychology ; Humans ; Intracellular Calcium-Sensing Proteins - agonists ; Intracellular Calcium-Sensing Proteins - antagonists & inhibitors ; Intracellular Calcium-Sensing Proteins - metabolism ; Medical sciences ; Orthopedics ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Osteoblasts - pathology ; Osteocytes - drug effects ; Osteocytes - metabolism ; Osteocytes - pathology ; Osteoporosis ; Osteoporosis - drug therapy ; Osteoporosis - metabolism ; Osteoporosis - pathology ; Osteoporosis. Osteomalacia. Paget disease ; Receptors, Calcium-Sensing - agonists ; Receptors, Calcium-Sensing - antagonists & inhibitors ; Receptors, Calcium-Sensing - metabolism ; Strontium ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Bone (New York, N.Y.), 2010-03, Vol.46 (3), p.571-576</ispartof><rights>Elsevier Inc.</rights><rights>2009 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-dda554a9fcf760b062003cd3b17022e993ff51f17d53e2b1dc6d12c15c675583</citedby><cites>FETCH-LOGICAL-c538t-dda554a9fcf760b062003cd3b17022e993ff51f17d53e2b1dc6d12c15c675583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S8756328209017852$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22592858$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19660583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marie, Pierre J</creatorcontrib><title>The calcium-sensing receptor in bone cells: A potential therapeutic target in osteoporosis</title><title>Bone (New York, N.Y.)</title><addtitle>Bone</addtitle><description>Abstract 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 target the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone cells</subject><subject>Calcium-sensing receptor</subject><subject>Diseases of the osteoarticular system</subject><subject>Drug Delivery Systems - methods</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Intracellular Calcium-Sensing Proteins - agonists</subject><subject>Intracellular Calcium-Sensing Proteins - antagonists & inhibitors</subject><subject>Intracellular Calcium-Sensing Proteins - metabolism</subject><subject>Medical sciences</subject><subject>Orthopedics</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoblasts - pathology</subject><subject>Osteocytes - drug effects</subject><subject>Osteocytes - metabolism</subject><subject>Osteocytes - pathology</subject><subject>Osteoporosis</subject><subject>Osteoporosis - drug therapy</subject><subject>Osteoporosis - metabolism</subject><subject>Osteoporosis - pathology</subject><subject>Osteoporosis. Osteomalacia. Paget disease</subject><subject>Receptors, Calcium-Sensing - agonists</subject><subject>Receptors, Calcium-Sensing - antagonists & inhibitors</subject><subject>Receptors, Calcium-Sensing - metabolism</subject><subject>Strontium</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>8756-3282</issn><issn>1873-2763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EotvCH-CAckGcEvyx_kKoUlVRQKrEgT1xsRxn0nrJ2sF2kPrvcdgVSBzg5MszM36fGYReENwRTMSbfdfHAB3FWHdYdljRR2hDlGQtlYI9RhsluWgZVfQMnee8xxgzLclTdEa0EJgrtkFfd_fQODs5vxzaDCH7cNckcDCXmBofmnVE42Ca8tvmqpljgVC8nZpyD8nOsBTvmmLTHZSVjrlAnGOK2edn6MlopwzPT-8F2t28311_bG8_f_h0fXXbOs5UaYfBcr61enSjFLjHouZhbmA9kZhS0JqNIycjkQNnQHsyODEQ6gh3QvKa4QK9PradU_y-QC7m4PP6YRsgLtkoWS1opbf_JSXbUk01EZWkR9LVJDnBaObkDzY9GILN6t7szSrGrO4Nlqa6r0UvT-2X_gDDn5KT7Aq8OgE2V-VjssH5_JujlGuqfiV6d-SgWvvhIZnsPAQHg6-bKWaI_t__uPyr3E0--DrxGzxA3sclhboPQ0ymBpsv65WsR4I1JlJxyn4CU_C3TQ</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Marie, Pierre J</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope></search><sort><creationdate>20100301</creationdate><title>The calcium-sensing receptor in bone cells: A potential therapeutic target in osteoporosis</title><author>Marie, Pierre J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-dda554a9fcf760b062003cd3b17022e993ff51f17d53e2b1dc6d12c15c675583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone cells</topic><topic>Calcium-sensing receptor</topic><topic>Diseases of the osteoarticular system</topic><topic>Drug Delivery Systems - methods</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Intracellular Calcium-Sensing Proteins - agonists</topic><topic>Intracellular Calcium-Sensing Proteins - antagonists & inhibitors</topic><topic>Intracellular Calcium-Sensing Proteins - metabolism</topic><topic>Medical sciences</topic><topic>Orthopedics</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoblasts - pathology</topic><topic>Osteocytes - drug effects</topic><topic>Osteocytes - metabolism</topic><topic>Osteocytes - pathology</topic><topic>Osteoporosis</topic><topic>Osteoporosis - drug therapy</topic><topic>Osteoporosis - metabolism</topic><topic>Osteoporosis - pathology</topic><topic>Osteoporosis. Osteomalacia. Paget disease</topic><topic>Receptors, Calcium-Sensing - agonists</topic><topic>Receptors, Calcium-Sensing - antagonists & inhibitors</topic><topic>Receptors, Calcium-Sensing - metabolism</topic><topic>Strontium</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marie, Pierre J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Bone (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marie, Pierre J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The calcium-sensing receptor in bone cells: A potential therapeutic target in osteoporosis</atitle><jtitle>Bone (New York, N.Y.)</jtitle><addtitle>Bone</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>46</volume><issue>3</issue><spage>571</spage><epage>576</epage><pages>571-576</pages><issn>8756-3282</issn><eissn>1873-2763</eissn><abstract>Abstract 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 target the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19660583</pmid><doi>10.1016/j.bone.2009.07.082</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Bone cells Calcium-sensing receptor Diseases of the osteoarticular system Drug Delivery Systems - methods Fundamental and applied biological sciences. Psychology Humans Intracellular Calcium-Sensing Proteins - agonists Intracellular Calcium-Sensing Proteins - antagonists & inhibitors Intracellular Calcium-Sensing Proteins - metabolism Medical sciences Orthopedics Osteoblasts - drug effects Osteoblasts - metabolism Osteoblasts - pathology Osteocytes - drug effects Osteocytes - metabolism Osteocytes - pathology Osteoporosis Osteoporosis - drug therapy Osteoporosis - metabolism Osteoporosis - pathology Osteoporosis. Osteomalacia. Paget disease Receptors, Calcium-Sensing - agonists Receptors, Calcium-Sensing - antagonists & inhibitors Receptors, Calcium-Sensing - metabolism Strontium Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | The calcium-sensing receptor in bone cells: A potential therapeutic target in osteoporosis |
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