{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T07:08:31Z","timestamp":1773472111783,"version":"3.50.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2014,1,20]],"date-time":"2014-01-20T00:00:00Z","timestamp":1390176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0086629","type":"journal-article","created":{"date-parts":[[2014,1,20]],"date-time":"2014-01-20T21:43:47Z","timestamp":1390254227000},"page":"e86629","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":41,"title":["Bcl2 Deficiency Activates FoxO through Akt Inactivation and Accelerates Osteoblast Differentiation"],"prefix":"10.1371","volume":"9","author":[{"given":"Takeshi","family":"Moriishi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisato","family":"Komori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Rokutanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihide","family":"Tsujimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izumi","family":"Asahina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihisa","family":"Komori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,1,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1359\/jbmr.070518","article-title":"Quantifying osteoblast and osteocyte apoptosis: challenges and rewards","volume":"22","author":"RL Jilka","year":"2007","journal-title":"J Bone Miner Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1210\/en.2003-0990","article-title":"Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength","volume":"145","author":"CA O'Brien","year":"2004","journal-title":"Endocrinology"},{"key":"ref3","first-page":"719","article-title":"Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity","volume":"104","author":"S Kousteni","year":"2001","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S8756-3282(00)00309-4","article-title":"In vivo regulation of apoptosis in metaphyseal trabecular bone of young rats by synthetic human parathyroid hormone (1\u201334) fragment","volume":"27","author":"D Stanislaus","year":"2000","journal-title":"Bone"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1210\/endo.140.11.7135","article-title":"Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro","volume":"140","author":"A Gohel","year":"1999","journal-title":"Endocrinology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1172\/JCI2799","article-title":"Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone","volume":"102","author":"RS Weinstein","year":"1998","journal-title":"J Clin Invest"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI6800","article-title":"Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin","volume":"104","author":"LI Plotkin","year":"1999","journal-title":"J Clin Invest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1172\/JCI6610","article-title":"Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone","volume":"104","author":"RL Jilka","year":"1999","journal-title":"J Clin Invest"},{"key":"ref9","first-page":"3128","article-title":"The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone","volume":"82","author":"A Tomkinson","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/jcp.10254","article-title":"Cell death regulation by the Bcl-2 protein family in the mitochondria","volume":"195","author":"Y Tsujimoto","year":"2003","journal-title":"J Cell Physiol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/jb\/mvm104","article-title":"FOXO Transcription Factors in the Regulatory Networks of Longevity","volume":"141","author":"H Daitoku","year":"2007","journal-title":"J Biochem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/ni.1784","article-title":"The cunning little vixen: Foxo and the cycle of life and death","volume":"10","author":"SM Hedrick","year":"2009","journal-title":"Nat Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB Signaling: Navigating Downstream","volume":"129","author":"BD Manning","year":"2007","journal-title":"Cell"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/377646a0","article-title":"Induction of the growth inhibitor IGF-binding protein 3 by p53","volume":"377","author":"L Buckbinder","year":"1995","journal-title":"Nature"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1097-2765(01)00323-9","article-title":"Regulation of PTEN transcription by p53","volume":"8","author":"V Stambolic","year":"2001","journal-title":"Mol Cell"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"a001057","DOI":"10.1101\/cshperspect.a001057","article-title":"p53 regulation of the IGF-1\/AKT\/mTOR pathways and the endosomal compartment","volume":"2","author":"Z Feng","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cmet.2009.12.009","article-title":"FoxO-Mediated Defense against Oxidative Stress in Osteoblasts Is Indispensable for Skeletal Homeostasis in Mice","volume":"11","author":"E Ambrogini","year":"2010","journal-title":"Cell Metabol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cmet.2010.01.001","article-title":"FoxO1 Is a Positive Regulator of Bone Formation by Favoring Protein Synthesis and Resistance to Oxidative Stress in Osteoblasts","volume":"11","author":"M-T Rached","year":"2010","journal-title":"Cell Metabol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"31055","DOI":"10.1074\/jbc.M109.079962","article-title":"Foxo1, a Novel Regulator of Osteoblast Differentiation and Skeletogenesis","volume":"285","author":"CC Teixeira","year":"2010","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.bone.2011.01.019","article-title":"FOXO1 modulates osteoblast differentiation","volume":"48","author":"MF Siqueira","year":"2011","journal-title":"Bone"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1359\/jbmr.071211","article-title":"Role of Bcl2 in Osteoclastogenesis and PTH Anabolic Actions in Bone","volume":"23","author":"J Yamashita","year":"2008","journal-title":"J Bone Miner Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"36659","DOI":"10.1074\/jbc.M109.016915","article-title":"Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts","volume":"284","author":"Y Nagase","year":"2009","journal-title":"J Biol Chem"},{"key":"ref23","first-page":"e40143","article-title":"Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis. PLoS ONE","volume":"7(6)","author":"T Moriishi","year":"2012"},{"key":"ref24","first-page":"354","article-title":"bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine","volume":"55","author":"S Kamada","year":"1995","journal-title":"Cancer Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/(SICI)1097-0177(199904)214:4<279::AID-AJA1>3.0.CO;2-W","article-title":"Maturational disturbance of chondrocytes in Cbfa1-deficient mice","volume":"214","author":"M Inada","year":"1999","journal-title":"Dev Dyn"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1101\/gad.1174704","article-title":"Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog","volume":"18","author":"CA Yoshida","year":"2004","journal-title":"Genes Dev"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0167-4781(91)90014-D","article-title":"Specific hybridization probes for mouse type I,II,III and IX collagen mRNAs","volume":"1089","author":"M Mets\u00e4ranta","year":"1991","journal-title":"Biochim Biophys Acta"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1267\/ahc.26.303","article-title":"Method for detecting the expression of bone matrix protein by in situ hybridization using decalcified mineralized tissue","volume":"26","author":"S Nomura","year":"1993","journal-title":"Acta Histochem Cytochem"},{"key":"ref29","first-page":"27","article-title":"Expression of mRNA of murine bone-related proteins in ectopic bone induced by murine bone morphogenetic protein-4. Cell Tissue Res","volume":"277","author":"S Hirota","year":"1994"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0092-8674(00)80258-5","article-title":"Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts","volume":"89","author":"T Komori","year":"1997","journal-title":"Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"20814","DOI":"10.1074\/jbc.M500528200","article-title":"The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling","volume":"280","author":"C Skurk","year":"2005","journal-title":"J Biol Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"26729","DOI":"10.1074\/jbc.C200256200","article-title":"FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress","volume":"277(30)","author":"Y Furukawa-Hibi","year":"2002","journal-title":"J Biol Chem 26"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1002\/dvdy.21187","article-title":"Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency","volume":"236(7)","author":"Z Maruyama","year":"2007","journal-title":"Dev Dyn"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.devcel.2010.07.010","article-title":"Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels","volume":"19(2)","author":"C Maes","year":"2010","journal-title":"Dev Cell 17"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"14057","DOI":"10.1073\/pnas.0406286101","article-title":"p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1","volume":"101","author":"H You","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"13987","DOI":"10.1074\/jbc.M901758200","article-title":"MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation","volume":"284","author":"W Fu","year":"2009","journal-title":"J Biol Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.cellbi.2009.04.017","article-title":"P53 negatively regulates the transcriptional activity of FOXO3a under oxidative stress","volume":"33","author":"Y Miyaguchi","year":"2009","journal-title":"Cell Biol Int"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/hep.23746","article-title":"Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice","volume":"52","author":"S Kurinna","year":"2010","journal-title":"Hepatology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1038\/onc.2011.35","article-title":"The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor","volume":"30","author":"VM Renault","year":"2011","journal-title":"Oncogene"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"10334","DOI":"10.1074\/jbc.M808848200","article-title":"The Transcription of FOXO Genes Is Stimulated by FOXO3 and Repressed by Growth Factors","volume":"284","author":"A Essaghir","year":"2009","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1083\/jcb.200508130","article-title":"Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling","volume":"172","author":"CJ Lengner","year":"2006","journal-title":"J Cell Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1083\/jcb.200507106","article-title":"p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling","volume":"172","author":"X Wang","year":"2006","journal-title":"J Cell Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0092-8674(93)80065-M","article-title":"Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair","volume":"75","author":"DJ Veis","year":"1993","journal-title":"Cell"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/sj.cdd.4401987","article-title":"BCL2 family in DNA damage and cell cycle control","volume":"13","author":"S Zinkel","year":"2006","journal-title":"Cell Death Differ"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"9545","DOI":"10.1073\/pnas.93.18.9545","article-title":"Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation","volume":"93","author":"GP Linette","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"6991","DOI":"10.1002\/j.1460-2075.1996.tb01091.x","article-title":"Bax alpha perturbs T cell development and affects cell cycle entry of T cells","volume":"15","author":"HJ Brady","year":"1996","journal-title":"EMBO J"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.4049\/jimmunol.162.9.5374","article-title":"Bcl-2-Induced Changes in E2F Regulatory Complexes Reveal the Potential for Integrated Cell Cycle and Cell Death Functions","volume":"162","author":"EF Lind","year":"1999","journal-title":"J Immunol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1128\/MCB.20.13.4745-4753.2000","article-title":"Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation","volume":"20","author":"G Vairo","year":"2000","journal-title":"Mol Cell Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"6257","DOI":"10.1073\/pnas.092672899","article-title":"bcl-2 overexpression promotes myocyte proliferation","volume":"99","author":"F Limana","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1042\/BST0340722","article-title":"FOXO transcription factors: key regulators of cell fate","volume":"34","year":"2006","journal-title":"Biochem Soc Trans"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0086629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T22:59:09Z","timestamp":1688943549000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0086629"}},"subtitle":[],"editor":[{"given":"Irina V.","family":"Lebedeva","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,1,20]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0086629","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,20]]}}}