Control of bone mass and remodeling by PTH receptor signaling in osteocytes. Export

@article{citeulike:3123979, abstract = {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.}, author = {O'Brien, Charles A. and Plotkin, Lilian I. and Galli, Carlo and Goellner, Joseph J. and Gortazar, Arancha R. and Allen, Matthew R. and Robling, Alexander G. and Bouxsein, Mary and Schipani, Ernestina and Turner, Charles H. and Jilka, Robert L. and Weinstein, Robert S. and Manolagas, Stavros C. and Bellido, Teresita}, citeulike-article-id = {3123979}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0002942}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18698360}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18698360}, citeulike-linkout-3 = {http://scholar.google.com/scholar?cluster=3565658012740886222}, day = {13}, doi = {10.1371/journal.pone.0002942}, issn = {1932-6203}, journal = {PloS one}, keywords = {osteocyte, pth, wnt\_osteo}, number = {8}, pages = {e2942+}, posted-at = {2009-10-28 17:49:30}, priority = {2}, publisher = {Public Library of Science}, title = {Control of bone mass and remodeling by PTH receptor signaling in osteocytes.}, url = {http://dx.doi.org/10.1371/journal.pone.0002942}, volume = {3}, year = {2008} }

TY - JOUR ID - citeulike:3123979 L3 - citeulike-article-id:3123979 N2 - 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. IS - 8 JF - PloS one SN - 1932-6203 TI - Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PB - Public Library of Science VL - 3 SP - e2942 KW - osteocyte KW - pth KW - wnt_osteo AU - O'Brien, Charles AU - Plotkin, Lilian AU - Galli, Carlo AU - Goellner, Joseph AU - Gortazar, Arancha AU - Allen, Matthew AU - Robling, Alexander AU - Bouxsein, Mary AU - Schipani, Ernestina AU - Turner, Charles AU - Jilka, Robert AU - Weinstein, Robert AU - Manolagas, Stavros AU - Bellido, Teresita PY - 2008//13/ UR - http://dx.doi.org/10.1371/journal.pone.0002942 ER -