{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T20:39:13Z","timestamp":1781987953417,"version":"3.54.5"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2012,7,13]],"date-time":"2012-07-13T00:00:00Z","timestamp":1342137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Class IA phosphatidylinositol 3-kinases (PI3Ks) are activated by growth factor receptors and regulate a wide range of cellular processes. In osteoclasts, they are activated downstream of \u03b1v\u03b23 integrin and colony-stimulating factor-1 receptor (c-Fms), which are involved in the regulation of bone-resorbing activity. The physiological relevance of the in vitro studies using PI3K inhibitors has been of limited value, because they inhibit all classes of PI3K. Here, we show that the osteoclast-specific deletion of the p85 genes encoding the regulatory subunit of the class IA PI3K results in an osteopetrotic phenotype caused by a defect in the bone-resorbing activity of osteoclasts. Class IA PI3K is required for the ruffled border formation and vesicular transport, but not for the formation of the sealing zone. p85\u03b1\/\u03b2 doubly deficient osteoclasts had a defect in macrophage colony-stimulating factor (M-CSF)\u2013induced protein kinase B (Akt) activation and the introduction of constitutively active Akt recovered the bone-resorbing activity. Thus, the class IA PI3K-Akt pathway regulates the cellular machinery crucial for osteoclastic bone resorption, and may provide a molecular basis for therapeutic strategies against bone diseases. \u00a9 2013 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.1703","type":"journal-article","created":{"date-parts":[[2012,7,14]],"date-time":"2012-07-14T04:46:50Z","timestamp":1342241210000},"page":"2464-2475","source":"Crossref","is-referenced-by-count":37,"title":["Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B\u2013mediated vesicle transport"],"prefix":"10.1093","volume":"27","author":[{"given":"Masahiro","family":"Shinohara","sequence":"first","affiliation":[{"name":"Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo, Japan"},{"name":"Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironari","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuho","family":"Kadono","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyasu","family":"Iwasawa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuichi","family":"Nagase","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohjiro","family":"Ueki","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Metabolic Diseases, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kadowaki","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Metabolic Diseases, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Immunology, Akita University School of Medicine, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Kato","sequence":"additional","affiliation":[{"name":"Laboratory of Nuclear Signaling, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Matsumoto 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