{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:31:42Z","timestamp":1778038302062,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AR065445"],"award-info":[{"award-number":["1R01AR065445"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012615","name":"UTHealth","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009339","name":"Steadman Philippon Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The dystrophin\u2212\/\u2212\/utrophin\u2212\/\u2212\/ double knockout (dKO-Hom) mouse is a murine model of human Duchenne muscular dystrophy. This study investigated the bone and muscle abnormalities of dKO-Hom mouse and mechanisms. We collected bone and skeletal muscle samples from control mice and three muscular dystrophic mouse models at different ages and performed micro-computer tomography and histological analyses of both bone and skeletal muscle tissues. Serum receptor activator of nuclear factor kappa-\u0392 ligand (RANKL) and sclerostin (SOST) levels, osteoclastogenesis and serum proteomics were also analyzed. Our results indicated that dKO-Hom mice developed skeletal muscle histopathologies by 5\u00a0days of age, whereas bone abnormalities developed at 4\u00a0weeks of age. Furthermore, our results indicated that the numbers of osteoblasts and osteoclasts were decreased in the proximal tibia and spine trabecular bone of dKO-Hom mice compared to wild-type (WT) mice, which correlated with a significant reduction in serum RANKL levels. The number of tibia cortical osteocytes also decreased, whereas serum SOST levels increased significantly in dKO-Hom mice than WT mice. Osteoblastic number was significantly lower, but osteoclast number increased, in the spine L6 of dKO-Hom mice than WT mice at 6\u00a0weeks of age, resulting in a decrease in bone formation and an increase in bone resorption. Serum proteomics results revealed abnormal proteome profiles in dKO-Hom mice compared to control mice. In conclusion, our study elucidated the timing of development of bone and muscle abnormalities. The bone abnormalities in dKO-Hom mice are correlated with lower serum RANKL and higher SOST levels that resulted in dysregulation of osteogenesis and osteoclastogenesis and bone loss.<\/jats:p>","DOI":"10.1093\/hmg\/ddz012","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T12:19:47Z","timestamp":1548418787000},"page":"1738-1751","source":"Crossref","is-referenced-by-count":19,"title":["Systemic investigation of bone and muscle abnormalities in dystrophin\/utrophin double knockout mice during postnatal development and the mechanisms"],"prefix":"10.1093","volume":"28","author":[{"given":"Xueqin","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA"},{"name":"Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, USA"},{"name":"Steadman Philippon Research Institute, Vail, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Amra","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuying","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haizi","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnny","family":"Huard","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA"},{"name":"Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, USA"},{"name":"Steadman Philippon Research Institute, Vail, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,28]]},"reference":[{"key":"2020070813041196100_ref1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0092-8674(87)90504-6","article-title":"Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals","volume":"50","author":"Koenig","year":"1987","journal-title":"Cell"},{"key":"2020070813041196100_ref2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1126\/science.3659917","article-title":"Conservation of the Duchenne muscular dystrophy gene in mice and humans","volume":"238","author":"Hoffman","year":"1987","journal-title":"Science"},{"key":"2020070813041196100_ref3","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: the protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"2020070813041196100_ref4","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1056\/NEJM198805263182104","article-title":"Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne\u2019s or Becker\u2019s muscular dystrophy","volume":"318","author":"Hoffman","year":"1988","journal-title":"N. 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