{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:04:44Z","timestamp":1793286284739,"version":"4.5.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01-AR071614"],"award-info":[{"award-number":["R01-AR071614"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,11,21]]},"abstract":"<jats:p>\n                    Bone regulates its mass and quality in response to diverse mechanical, hormonal, and local signals. The bone anabolic or catabolic responses to these signals are often received by osteocytes, which then coordinate the activity of osteoblasts and osteoclasts on bone surfaces. We previously established that calcium\/calmodulin-dependent kinase 2 (CaMKII) is required for osteocytes to respond to some bone anabolic cues in vitro. However, a role for CaMKII in bone physiology in vivo is largely undescribed. Here, we show that conditional codeletion of the most abundant isoforms of CaMKII (delta and gamma) in mature osteoblasts and osteocytes [Ocn-cre:\n                    <jats:italic>Camk2d<\/jats:italic>\n                    \/\n                    <jats:italic>Camk2g<\/jats:italic>\n                    double-knockout (dCKO)] caused severe osteopenia in both cortical and trabecular compartments by 8 wk of age. In addition to having less bone mass, dCKO bones are of worse quality, with significant deficits in mechanical properties, and a propensity to fracture. This striking skeletal phenotype is multifactorial, including diminished osteoblast activity, increased osteoclast activity, and altered phosphate homeostasis both systemically and locally. These dCKO mice exhibited decreased circulating phosphate (hypophosphatemia) and increased expression of the phosphate-regulating hormone fibroblast growth factor 23. Additionally, dCKO mice expressed less bone-derived tissue nonspecific alkaline phosphatase protein than control mice. Consistent with altered phosphate homeostasis, we observed that dCKO bones were hypo-mineralized with prominent osteoid seams, analogous to the phenotypes of mice with hypophosphatemia. Altogether, these data reveal a fundamental role for osteocyte CaMKII\u03b4 and CaMKII\u03b3 in the maintenance of bone mass and bone quality and link osteoblast\/osteocyte CaMKII to phosphate homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2304492120","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T13:27:09Z","timestamp":1700227629000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Osteoblast-lineage calcium\/calmodulin-dependent kinase 2 delta and gamma regulates bone mass and quality"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-0366","authenticated-orcid":false,"given":"Jenna M.","family":"Leser","sequence":"first","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia M.","family":"Torre","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-2628","authenticated-orcid":false,"given":"Nicole R.","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyue","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-3369","authenticated-orcid":false,"given":"Heather V.","family":"Buck","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8331-7772","authenticated-orcid":false,"given":"Joe","family":"Kodama","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-6614","authenticated-orcid":false,"given":"Satoru","family":"Otsuru","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-4694","authenticated-orcid":false,"given":"Joseph P.","family":"Stains","sequence":"additional","affiliation":[{"name":"Department of Othopaedics, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.115971"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2020"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.320"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1546-x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/jfmk6010028"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aan5748"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64393"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115356"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-020-01176-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84658-6"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00624-2"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-051421-111814"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0108-3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01272-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14454"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2017.07.003"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412680200"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09653-5"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.4251","article-title":"In vitro fluid shear stress induced sclerostin degradation and CaMKII activation in osteocytes","volume":"11","author":"Gould N.","year":"2021","unstructured":"N. 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