Control of bone mass and remodeling by PTH receptor signaling in osteocytes
Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone lo...
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| creator | O'Brien, Charles A Plotkin, Lilian I Galli, Carlo Goellner, Joseph J Gortazar, Arancha R Allen, Matthew R Robling, Alexander G Bouxsein, Mary Schipani, Ernestina Turner, Charles H Jilka, Robert L Weinstein, Robert S Manolagas, Stavros C Bellido, Teresita |
| description | Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively. |
| doi_str_mv | 10.1371/journal.pone.0002942 |
| format | Article |
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However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0002942</identifier><identifier>PMID: 18698360</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Biocompatibility ; Biology ; Bone and Bones - anatomy & histology ; Bone and Bones - physiology ; Bone density ; Bone diseases ; Bone growth ; Bone loss ; Bone marrow ; Bone mass ; Bone remodeling ; Bone Remodeling - physiology ; Bone resorption ; Bone surgery ; Cell Biology/Cell Signaling ; Diabetes and Endocrinology/Bone and Mineral Metabolism ; Diabetes and Endocrinology/Endocrinology ; Endocrinology ; Extracellular Matrix Proteins - genetics ; Gene expression ; Genetic engineering ; Homeostasis ; Hormones ; Humans ; Kinases ; Ligands ; Low density lipoprotein ; LRP5 protein ; Mechanical stimuli ; Metabolism ; Mice ; Mice, Transgenic ; Osteoblasts ; Osteoblasts - cytology ; Osteoclasts - cytology ; Osteocytes ; Osteocytes - physiology ; Osteoporosis ; Parathyroid ; Parathyroid hormone ; Parathyroid hormones ; Phosphoproteins - genetics ; Physiology/Cell Signaling ; Physiology/Endocrinology ; Physiology/Integrative Physiology ; Proteins ; Receptor, Parathyroid Hormone, Type 1 - genetics ; Receptors, Parathyroid Hormone - physiology ; Signal Transduction - physiology ; SOST protein ; Transgenic mice ; Wnt protein</subject><ispartof>PloS one, 2008-08, Vol.3 (8), p.e2942-e2942</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 O'Brien et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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cytology</subject><subject>Osteoclasts - cytology</subject><subject>Osteocytes</subject><subject>Osteocytes - physiology</subject><subject>Osteoporosis</subject><subject>Parathyroid</subject><subject>Parathyroid hormone</subject><subject>Parathyroid hormones</subject><subject>Phosphoproteins - genetics</subject><subject>Physiology/Cell Signaling</subject><subject>Physiology/Endocrinology</subject><subject>Physiology/Integrative Physiology</subject><subject>Proteins</subject><subject>Receptor, Parathyroid Hormone, Type 1 - genetics</subject><subject>Receptors, Parathyroid Hormone - physiology</subject><subject>Signal Transduction - physiology</subject><subject>SOST protein</subject><subject>Transgenic mice</subject><subject>Wnt protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1rFDEUhgex2Fr9B6IDQsGLXfM1mcmNUBa1i4WKVm9Dkklms2Qm2yQj7r836452VwQlFwknz3lP8p5TFM8gmENcw9drP4ZBuPnGD3oOAECMoAfFGWQYzSgC-OHB-bR4HOMagAo3lD4qTmFDWYMpOCs-LPyQgnelN6XMSmUvYizF0JZB977Vzg5dKbflx9urHFF6k3woo-1y5d2NHUofk_Zqm3R8UpwY4aJ-Ou3nxZd3b28XV7Prm_fLxeX1TFGG08xUhiAIqDBSUqJFIykzBgCFCDSAUKFp3SJVYY0lk0YAI2SDcc0QrvK7ET4vXux1N85HPvkQOcQQIVYjzDKx3BOtF2u-CbYXYcu9sPxnwIeOi5CscpojUDGV6xAhK6IwaVDdkNYYChSEbdVkrTdTtVH2ulU6-yXckejxzWBXvPPfOCIMVs1O4GISCP5u1DHx3kalnROD9mPkNDcOsxr8E8ymVTUkOIMv_wD_bsJ8T3Ui_9MOxufnqbxa3VuVe21sjl-SGlFMIYE54dVRQmaS_p46McbIl58__T978_WYvThgV1q4tIrejcn6IR6DZA-q4GMM2vx2GQK-G_pf_-S7oefT0Oe054cduk-aphz_AEOj_CY</recordid><startdate>20080813</startdate><enddate>20080813</enddate><creator>O'Brien, Charles A</creator><creator>Plotkin, Lilian I</creator><creator>Galli, Carlo</creator><creator>Goellner, Joseph J</creator><creator>Gortazar, Arancha R</creator><creator>Allen, Matthew R</creator><creator>Robling, Alexander G</creator><creator>Bouxsein, Mary</creator><creator>Schipani, Ernestina</creator><creator>Turner, Charles H</creator><creator>Jilka, Robert L</creator><creator>Weinstein, Robert S</creator><creator>Manolagas, Stavros C</creator><creator>Bellido, Teresita</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7QP</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20080813</creationdate><title>Control of bone mass and remodeling by PTH receptor signaling in osteocytes</title><author>O'Brien, Charles A ; Plotkin, Lilian I ; Galli, Carlo ; Goellner, Joseph J ; Gortazar, Arancha R ; Allen, Matthew R ; Robling, Alexander G ; Bouxsein, Mary ; Schipani, Ernestina ; Turner, Charles H ; Jilka, Robert L ; Weinstein, Robert S ; Manolagas, Stavros C ; Bellido, Teresita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c693t-f5f42106afbb64ea8b69ff00c241f046ae67d2c53e3b9bfa0fab8337923586923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Bone and Bones - 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However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. 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| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis Biocompatibility Biology Bone and Bones - anatomy & histology Bone and Bones - physiology Bone density Bone diseases Bone growth Bone loss Bone marrow Bone mass Bone remodeling Bone Remodeling - physiology Bone resorption Bone surgery Cell Biology/Cell Signaling Diabetes and Endocrinology/Bone and Mineral Metabolism Diabetes and Endocrinology/Endocrinology Endocrinology Extracellular Matrix Proteins - genetics Gene expression Genetic engineering Homeostasis Hormones Humans Kinases Ligands Low density lipoprotein LRP5 protein Mechanical stimuli Metabolism Mice Mice, Transgenic Osteoblasts Osteoblasts - cytology Osteoclasts - cytology Osteocytes Osteocytes - physiology Osteoporosis Parathyroid Parathyroid hormone Parathyroid hormones Phosphoproteins - genetics Physiology/Cell Signaling Physiology/Endocrinology Physiology/Integrative Physiology Proteins Receptor, Parathyroid Hormone, Type 1 - genetics Receptors, Parathyroid Hormone - physiology Signal Transduction - physiology SOST protein Transgenic mice Wnt protein |
| title | Control of bone mass and remodeling by PTH receptor signaling in osteocytes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T08%3A17%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Control%20of%20bone%20mass%20and%20remodeling%20by%20PTH%20receptor%20signaling%20in%20osteocytes&rft.jtitle=PloS%20one&rft.au=O'Brien,%20Charles%20A&rft.date=2008-08-13&rft.volume=3&rft.issue=8&rft.spage=e2942&rft.epage=e2942&rft.pages=e2942-e2942&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0002942&rft_dat=%3Cgale_plos_%3EA472636141%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312297239&rft_id=info:pmid/18698360&rft_galeid=A472636141&rft_doaj_id=oai_doaj_org_article_2059cb9b4ab54c3482784dff60c11d58&rfr_iscdi=true |