{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:37:27Z","timestamp":1789951047505,"version":"4.0.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T00:00:00Z","timestamp":1470700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ellenberg Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0160684","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T17:39:18Z","timestamp":1470764358000},"page":"e0160684","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Del1 Knockout Mice Developed More Severe Osteoarthritis Associated with Increased Susceptibility of Chondrocytes to Apoptosis"],"prefix":"10.1371","volume":"11","author":[{"given":"Zhen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha C.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namrata J.","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander W.","family":"Hsing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie F.","family":"LaRussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Fattakhov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vania","family":"Rashidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Yun","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Choo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingju","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Mathy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Longaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold H.","family":"Dauskardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Helms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,8,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1056\/NEJMcp051726","article-title":"Clinical practice. Osteoarthritis of the knee","volume":"354","author":"DT Felson","year":"2006","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/jor.21359","article-title":"Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention","volume":"29","author":"DD Anderson","year":"2011","journal-title":"J Orthop Res"},{"key":"ref3","first-page":"237","article-title":"The role of cytokines in osteoarthritis pathophysiology","volume":"39","author":"JC Fernandes","year":"2002","journal-title":"Biorheology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1136\/jmg.34.12.1024","article-title":"Genetic linkage analysis of 14 candidate gene loci in a family with autosomal dominant osteoarthritis without dysplasia","volume":"34","author":"I Meulenbelt","year":"1997","journal-title":"J Med Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/2005","article-title":"A functional polymorphism in the 5&apos; UTR of GDF5 is associated with susceptibility to osteoarthritis","volume":"39","author":"Y Miyamoto","year":"2007","journal-title":"Nat Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.ajhg.2008.04.006","article-title":"Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis","volume":"82","author":"AM Valdes","year":"2008","journal-title":"Am J Hum Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/01.bor.0000240369.39713.af","article-title":"Animal models of osteoarthritis: lessons learned while seeking the &quot;Holy Grail&quot;","volume":"18","author":"LG Ameye","year":"2006","journal-title":"Curr Opin Rheumatol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1002\/1529-0131(200106)44:6<1455::AID-ART241>3.0.CO;2-J","article-title":"Matrix metalloproteinases and aggrecanases cleave aggrecan in different zones of normal cartilage but colocalize in the development of osteoarthritic lesions in STR\/ort mice","volume":"44","author":"MG Chambers","year":"2001","journal-title":"Arthritis Rheum"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nature03369","article-title":"Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis","volume":"434","author":"SS Glasson","year":"2005","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nm.2146","article-title":"Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development","volume":"16","author":"T Saito","journal-title":"Nat Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nm.2153","article-title":"Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction","volume":"16","author":"S Yang","journal-title":"Nat Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e4543","DOI":"10.1371\/journal.pone.0004543","article-title":"C\/EBPbeta Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57","volume":"4","author":"M Hirata","year":"2009","journal-title":"PLoS One"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/nm.2055","article-title":"Modulating hedgehog signaling can attenuate the severity of osteoarthritis","volume":"15","author":"AC Lin","year":"2009","journal-title":"Nat Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/art.27357","article-title":"Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic knees","volume":"62","author":"LH Weng","journal-title":"Arthritis Rheum"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/art.37750","article-title":"Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model","volume":"65","author":"O Gabay","year":"2013","journal-title":"Arthritis Rheum"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.joca.2014.04.025","article-title":"Endoplasmic reticulum stress-induced apoptosis contributes to articular cartilage degeneration via C\/EBP homologous protein","volume":"22","author":"Y Uehara","year":"2014","journal-title":"Osteoarthritis Cartilage"},{"key":"ref17","first-page":"28","article-title":"Heritable diseases of cartilage caused by mutations in collagen genes","volume":"43","author":"CJ Williams","year":"1995","journal-title":"J Rheumatol Suppl"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1101\/gad.12.1.21","article-title":"Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor","volume":"12","author":"C Hidai","year":"1998","journal-title":"Genes Dev"},{"issue":"Suppl 3","key":"ref19","first-page":"S17","article-title":"The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"SS Glasson","journal-title":"Osteoarthritis Cartilage"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1128\/MCB.01342-10","article-title":"A pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition","volume":"31","author":"S Kumar","year":"2011","journal-title":"Mol Cell Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.matbio.2012.01.003","article-title":"Adhesion-modulating\/matricellular ECM protein families: a structural, functional and evolutionary appraisal","volume":"31","author":"DF Mosher","year":"2012","journal-title":"Matrix Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"31522","DOI":"10.1074\/jbc.M804234200","article-title":"Chondrocyte aggregation in suspension culture is GFOGER-GPP- and beta1 integrin-dependent","volume":"283","author":"A Gigout","year":"2008","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nm.3143","article-title":"Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis","volume":"19","author":"G Zhen","year":"2013","journal-title":"Nat Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/art.37755","article-title":"ADAM-10 is overexpressed in rheumatoid arthritis synovial tissue and mediates angiogenesis","volume":"65","author":"T Isozaki","year":"2013","journal-title":"Arthritis Rheum"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1002\/art.34602","article-title":"Dkk-1 promotes angiogenic responses and cartilage matrix proteinase secretion in synovial fibroblasts from osteoarthritic joints","volume":"64","author":"LH Weng","year":"2012","journal-title":"Arthritis Rheum"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"11101","DOI":"10.1074\/jbc.274.16.11101","article-title":"Del1 induces integrin signaling and angiogenesis by ligation of alphaVbeta3","volume":"274","author":"K Penta","year":"1999","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.surg.2011.07.013","article-title":"The angiogenic factor Del1 prevents apoptosis of endothelial cells through integrin binding","volume":"151","author":"Z Wang","year":"2012","journal-title":"Surgery"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1126\/science.1165218","article-title":"Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment","volume":"322","author":"EY Choi","year":"2008","journal-title":"Science"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/417182a","article-title":"Identification of a factor that links apoptotic cells to phagocytes","volume":"417","author":"R Hanayama","year":"2002","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.4049\/jimmunol.172.6.3876","article-title":"Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells","volume":"172","author":"R Hanayama","year":"2004","journal-title":"J Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1053\/joca.2000.0363","article-title":"The STR\/ort mouse and its use as a model of osteoarthritis","volume":"9","author":"RM Mason","year":"2001","journal-title":"Osteoarthritis Cartilage"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrrheum.2013.72","article-title":"Post-traumatic osteoarthritis: from mouse models to clinical trials","volume":"9","author":"CB Little","year":"2013","journal-title":"Nat Rev Rheumatol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"8709","DOI":"10.1128\/MCB.22.24.8709-8720.2002","article-title":"CYR61 (CCN1) Is Essential for Placental Development and Vascular Integrity","volume":"22","author":"FE Mo","year":"2002","journal-title":"Molecular and Cellular Biology"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1006\/dbio.1997.8766","article-title":"Cyr61, product of a growth factor-inducible immediate-early gene, regulates chondrogenesis in mouse limb bud mesenchymal cells","volume":"192","author":"M Wong","year":"1997","journal-title":"Dev Biol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1242\/dev.00505","article-title":"Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development","volume":"130","author":"S Ivkovic","year":"2003","journal-title":"Development"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/12699","article-title":"Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia","volume":"23","author":"JR Hurvitz","year":"1999","journal-title":"Nat Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1128\/MCB.25.1.414-421.2005","article-title":"WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice","volume":"25","author":"WE Kutz","year":"2005","journal-title":"Mol Cell Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.semarthrit.2005.01.013","article-title":"Osteoarthritis: an overview of the disease and its treatment strategies","volume":"35","author":"P Sarzi-Puttini","year":"2005","journal-title":"Semin Arthritis Rheum"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa052771","article-title":"Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis","volume":"354","author":"DO Clegg","year":"2006","journal-title":"N Engl J Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0160684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T07:58:23Z","timestamp":1589011103000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0160684"}},"subtitle":[],"editor":[{"given":"Jan Peter","family":"Tuckermann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,8,9]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0160684","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,9]]}}}