{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T07:01:30Z","timestamp":1780210890563,"version":"3.54.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/14950\u20104"],"award-info":[{"award-number":["2020\/14950\u20104"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["405939\/2021\u20103"],"award-info":[{"award-number":["405939\/2021\u20103"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["307698\/2021\u20101"],"award-info":[{"award-number":["307698\/2021\u20101"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["305033\/2022\u20100"],"award-info":[{"award-number":["305033\/2022\u20100"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.081812\/2024\u201000"],"award-info":[{"award-number":["88887.081812\/2024\u201000"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Agrin is an important factor in maintaining skeletal architecture. However, the role of osteoblast\u2010expressed agrin in bone tissue remains unexplored. Thus, we hypothesized that agrin\u2010deficient osteoblasts negatively affect bone tissue homeostasis by disrupting osteoblastic differentiation of mesenchymal stem cells (MSCs). To investigate this hypothesis, mice with deletion of agrin in Runx2\u2010expressing osteoblasts were generated using Runx2\u2010Cre mice. Microtomographic analyses revealed that agrin ablation in osteoblasts resulted in deleterious effects on the cortical bone of the femurs, leading to a tendency towards reduced bone stiffness, as indicated by the three\u2010point bending test. This negative impact of agrin\u2010deficient osteoblasts on bone tissue may be partially attributed to the reduced osteoblastic differentiation of MSCs derived from these mice, as evidenced by lower expression of osteoblastic marker genes and alkaline phosphatase activity. This disruption in osteoblastic differentiation is directly linked to agrin\u2010deficient osteoblasts, as demonstrated by diminished gene expression of agrin and its receptors in MSCs collected from these animals. Our findings highlight the role of osteoblast\u2010secreted agrin in maintaining long bone structure, mainly by promoting MSC differentiation into osteoblasts. The findings indicate that agrin could be an effective therapeutic target for treating bone loss\u2010related conditions, such as osteoporosis and aging.<\/jats:p>","DOI":"10.1002\/jcb.70094","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:20:36Z","timestamp":1780129236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Agrin Ablation in Osteoblasts Compromises Long Bone Structure and Osteoblastic Differentiation of Mesenchymal Stem Cells"],"prefix":"10.1002","volume":"127","author":[{"given":"Gabriela Camarneiro","family":"Siqueira","sequence":"first","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4466-0794","authenticated-orcid":false,"given":"Maria Paula Oliveira","family":"Gomes","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-5136","authenticated-orcid":false,"given":"Let\u00edcia Faustino","family":"Adolpho","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Ying Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola Singaretti","family":"Olveira","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Luisa Gon\u00e7alves","family":"Almeida","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger Rodrigo","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7716-106X","authenticated-orcid":false,"given":"Ana Paula","family":"Macedo","sequence":"additional","affiliation":[{"name":"Bioengineering Lab, Orthopedics and Anesthesiology Department, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Ramos","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Philosophy, Sciences and Letters at Ribeir\u00e3o Preto University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalberto Luiz","family":"Rosa","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0149-7189","authenticated-orcid":false,"given":"Marcio Mateus","family":"Beloti","sequence":"additional","affiliation":[{"name":"Bone Research Lab, Ribeir\u00e3o Preto School of Dentistry University of S\u00e3o Paulo Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650030509"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.278"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2527\/1999.77suppl_2190x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-08190-7"},{"key":"e_1_2_11_6_1","first-page":"387","article-title":"Bone Biology. II: Formation, Form, Modeling, Remodeling, and Regulation of Cell Function","volume":"45","author":"Buckwalter J. A.","year":"1996","journal-title":"Instructional Course Lectures"},{"key":"e_1_2_11_7_1","first-page":"197","article-title":"Origine Des Cellules Osseuses [Origin of Bone Cells (Author's Transl)]","volume":"11","author":"Vernejoul M. C.","year":"1982","journal-title":"La Nouvelle presse m\u00e9dicale"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001980070028"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.71"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80257-3"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.8.2891-2905.2001"},{"key":"e_1_2_11_12_1","first-page":"1430","article-title":"[CBFA1\/PEBP2 Alpha A]","volume":"56","author":"Komori T.","year":"1998","journal-title":"Nihon Rinsho: Japanese Journal of Clinical Medicine"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.05.014"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.180309597"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3254"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2427124122"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16934"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(98)00393-x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201241"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00248-8"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31115"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29674"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24614"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2019.110513"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25469"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3303com"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02814"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134676"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.002"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.05.012"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13573"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.70116"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22978"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207316"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-006-0258-2"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-021-03494-9"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.142551"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-21-0189"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-331272"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8695"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.2.213"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-025-00439-8"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32112"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3654"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.05.005"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax9086"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080311"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00948-6"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25073"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.4248\/BR201302003"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21202-7"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.70094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.70094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.70094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T06:56:53Z","timestamp":1780210613000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.70094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jcb.70094"],"URL":"https:\/\/doi.org\/10.1002\/jcb.70094","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70094"}}