{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:42:36Z","timestamp":1791265356560,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T00:00:00Z","timestamp":1350950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by the lack of dystrophin expression at the sarcolemma of muscle fibers. In addition, DMD patients acquire osteopenia, fragility fractures, and scoliosis indicating that a deficiency in skeletal homeostasis coexists but little is known about the effects of DMD on bone and other connective tissues within the musculoskeletal system. Recent evidence has emerged implicating adult stem cell dysfunction in DMD myopathogenesis. Given the common mesenchymal origin of muscle and bone, we sought to investigate bone and other musculoskeletal tissues in a DMD mouse model. Here, we report that <jats:italic>dystrophin\u2013utrophin<\/jats:italic> double knockout (<jats:italic>dko<\/jats:italic>) mice exhibit a spectrum of degenerative changes, outside skeletal muscle, in bone, articular cartilage, and intervertebral discs, in addition to reduced lifespan, muscle degeneration, spinal deformity, and cardiomyopathy previously reported. We also report these mice to have a reduced capacity for bone healing and exhibit spontaneous heterotopic ossification in the hind limb muscles. Therefore, we propose the <jats:italic>dko<\/jats:italic> mouse as a model for premature musculoskeletal aging and posit that a similar phenomenon may occur in patients with DMD. \u00a9 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 343\u2013349, 2013<\/jats:p>","DOI":"10.1002\/jor.22236","type":"journal-article","created":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T18:17:14Z","timestamp":1351016234000},"page":"343-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Dystrophin and utrophin \u201cdouble knockout\u201d dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities"],"prefix":"10.1002","volume":"31","author":[{"given":"Christian","family":"Isaac","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvydas","family":"Usas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshuai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam","family":"Vo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Huard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-200001000-00016"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200203000-00009"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90504-6"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198805263182104"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006972315739"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.039"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.05.014"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1214204"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.010"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114758"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.044"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07384"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01233096"},{"key":"e_1_2_6_15_2","first-page":"553","article-title":"Skeletal changes in children with neuromuscular disorders","volume":"101","author":"Hsu JD","year":"1982","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2002.tb00272.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/000992280304200408"},{"key":"e_1_2_6_18_2","first-page":"24","article-title":"Bone markers and bone mineral density in Duchenne muscular dystrophy","volume":"8","author":"Soderpalm AC","year":"2008","journal-title":"J Musculoskel Neuron Interact"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.F.00506"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.1.57"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040129"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.12.054"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080306"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(93)90084-N"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.20224"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.09.011"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2010.12.002"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.410"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.4.1189"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2662404"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(87)90219-X"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/110.2.269"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1988.tb00866.x"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(91)90340-9"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80532-2"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80533-4"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0030-5898(20)31137-8"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(81)90476-1"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-003-1443-y"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.05.008"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018627705273"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1301\/nr.2003.may.157-167"},{"key":"e_1_2_6_43_2","first-page":"66","article-title":"Sarcopenia and osteoporosis: a hazardous duet","volume":"28","author":"Crepaldi G","year":"2005","journal-title":"J Endocrinol Invest"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.7205\/MILMED-D-11-00061"},{"key":"e_1_2_6_45_2","first-page":"106","article-title":"Aging and osteoarthritis","volume":"76","author":"Bohatirchuk F","year":"1957","journal-title":"Can Med Assoc J"},{"key":"e_1_2_6_46_2","first-page":"49","article-title":"Osteoarthritis: diagnosis and treatment","volume":"85","author":"Sinusas K","year":"2012","journal-title":"Am Fam Physician"},{"key":"e_1_2_6_47_2","first-page":"122","article-title":"Gait and posture changes in the Duchenne muscular dystrophy child","volume":"288","author":"Hsu JD","year":"1993","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200902000-00006"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1159\/000046435"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2006.00603.x"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2010.03.002"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000231761.73859.2c"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-004-1702-6"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.036"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1611"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.22236","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.22236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T19:04:16Z","timestamp":1696878256000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.22236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,23]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/jor.22236"],"URL":"https:\/\/doi.org\/10.1002\/jor.22236","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,23]]},"assertion":[{"value":"2012-04-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}