{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:33:09Z","timestamp":1788845589174,"version":"build-2803163510"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Loss of bone mass and strength is a common problem of advanced age in humans. Defective bone is also a primary finding in osteogenesis imperfecta (OI), a genetic condition most commonly caused by autosomal dominant mutations in the type I collagen genes. Although altered collagen has been proposed to correlate with cellular processes that underlie aging, the causal relationships between them in vivo have not yet been completely explored. Whether aging plays a promoting role in OI development or whether OI contributes to aging, also remains unknown. The\n                    <jats:italic>PpiB<\/jats:italic>\n                    gene encodes cyclophilin B (CypB), a prolyl isomerase residing in the endoplasmic reticulum required for normal assembly of collagen. Germline deletion or mutations of CypB in mice or humans cause autosomal recessive OI (type IX). Here, we show that mice lacking CypB develop early onset of aging\u2010associated phenotypes, including kyphosis, fat reduction and weight loss, as well as abnormal teeth, skin, and muscle. Elevated senescence\u2010associated beta\u2010galactosidase (SA\u2010\u03b2\u2010Gal) activity was observed in fat tissues and in bone marrow\u2013derived multipotent stromal cells. Protein levels of the cyclin\u2010dependent kinase (cdk)\u2010inhibitor p21\u2010Cip1\/Waf1, a well known senescence marker, were significantly elevated in CypB\u2010deficient primary cells and mouse tissues. Importantly, loss of p21 in CypB knockout mice attenuated SA\u2010\u03b2\u2010Gal activity and delayed the development of kyphosis. In addition, less adipose tissue depot and higher SA\u2010\u03b2\u2010Gal activity were observed in a second OI model,\n                    <jats:italic>Cola2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>oim<\/jats:italic>\n                    <\/jats:sup>\n                    mutant mice. A potential upregulation of p21 was also revealed in a limited number of these mice. These findings suggest that some of the features in OI patients may be mediated in part through activation of the p21\u2010dependent pathway, one of which is closely associated with senescence and aging. This study provides new mechanistic insight into relationships between OI and aging and raises the possibility of using senolytics drugs to treat OI in the future. \u00a9 2022 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10674","type":"journal-article","created":{"date-parts":[[2022,8,20]],"date-time":"2022-08-20T01:49:20Z","timestamp":1660960160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Accelerated Aging in Cyclophilin B\u2013Deficient Mice Downstream of\n                    <scp>p21\u2010Cip1<\/scp>\n                    \/Waf1"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-5420","authenticated-orcid":false,"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine Mayo Clinic College of Medicine  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-9438","authenticated-orcid":false,"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Geriatric Medicine and Gerontology Mayo Clinic College of Medicine  Rochester MN USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic College of Medicine  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5940-6158","authenticated-orcid":false,"given":"Richard J.","family":"Bram","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine Mayo Clinic College of Medicine  Rochester MN USA"},{"name":"Department of Immunology Mayo Clinic College of Medicine  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-007-0023-z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2014.05.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-016-0083-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-20-0299"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(92)90200-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18189.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.5.1903"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.9.3741"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02237-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.05.014"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.14.8.0508"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000750"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.11.005"},{"issue":"3","key":"e_1_2_9_15_1","first-page":"797","article-title":"The process of ageing reflected by histological changes in the skin","volume":"54","author":"Bonta M","year":"2013","journal-title":"Rom J Morphol Embryol"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12155"},{"issue":"5","key":"e_1_2_9_17_1","first-page":"e00090","article-title":"Overexpression of MMP\u20107 increases collagen 1A2 in the aging kidney","volume":"1","author":"Oelusarz A","year":"2013","journal-title":"Physiol Rep"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/377552a0"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medengphy.2008.03.006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301578"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.764"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1701"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anpedi.2009.12.022"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2016.10.001"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00658.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.03.028"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2944"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15570"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.623175"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2005.07.011"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2017.1121"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2017.08.007"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-0771"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.04.017"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1937"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1395.036"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1382"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10674","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm4.10674","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T09:57:32Z","timestamp":1710410252000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/7479130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/jbm4.10674"],"URL":"https:\/\/doi.org\/10.1002\/jbm4.10674","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JBM4.10674\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10674\/v1\/review2","asserted-by":"object"}]},"ISSN":["2473-4039","2473-4039"],"issn-type":[{"value":"2473-4039","type":"print"},{"value":"2473-4039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]},"assertion":[{"value":"2022-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10674"}}