{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:07:10Z","timestamp":1792872430583,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"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\/100000945","name":"Pittsburgh Foundation","doi-asserted-by":"publisher","award":["AD2014-73915-12"],"award-info":[{"award-number":["AD2014-73915-12"]}],"id":[{"id":"10.13039\/100000945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000945","name":"Pittsburgh Foundation","doi-asserted-by":"publisher","award":["AD2017-91232"],"award-info":[{"award-number":["AD2017-91232"]}],"id":[{"id":"10.13039\/100000945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000945","name":"Pittsburgh Foundation","doi-asserted-by":"publisher","award":["AD2020-112747"],"award-info":[{"award-number":["AD2020-112747"]}],"id":[{"id":"10.13039\/100000945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Duchenne muscular dystrophy (DMD) is a severe X-linked inherited muscular disorder characterized by the loss of dystrophin. We have previously shown that monogene therapy using the mini-dystrophin gene improves muscle function in DMD. However, chronic inflammation plays an important role in progressive muscle degeneration in DMD as well. Vascular endothelial growth factor (VEGF) has been used to enhance muscle vasculature, reduce local inflammation and improve DMD muscle function. Temporalis muscles are the key skeletal muscles for mastication and loss of their function negatively affects DMD patient quality of life by reducing nutritional intake, but little is known about the pathology and treatment of the temporalis muscle in DMD. In this work, we tested the hypothesis that the combined delivery of the human mini-dystrophin and human VEGF genes to the temporalis muscles using separate recombinant adeno-associated viral (rAAV) vectors will synergistically improve muscle function and pathology in adult male dystrophin\/utrophin double-knockout (mdx\/utrn+\/\u2212) mice. The experimental mice were divided into four groups including: dystrophin + VEGF combined, dystrophin only, VEGF only and PBS control. After 2\u00a0months, gene expression and histological analysis of the temporalis muscles showed a synergistic improvement in temporalis muscle pathology and function coincident with increased restoration of dystrophin-associated protein complexes and nNOS in the dystrophin + VEGF combined group. We also observed significantly reduced inflammatory cell infiltration, central nucleation, and fibrosis in the dystrophin + VEGF combined group. We have demonstrated the efficacy of combined rAAV-mediated dystrophin and VEGF treatment of temporalis muscles in a DMD mouse model.<\/jats:p>","DOI":"10.1093\/hmg\/ddab120","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T10:49:16Z","timestamp":1620384556000},"page":"1349-1359","source":"Crossref","is-referenced-by-count":15,"title":["Combined gene therapy via VEGF and mini-dystrophin synergistically improves pathologies in temporalis muscle of dystrophin\/utrophin double knockout mice"],"prefix":"10.1093","volume":"30","author":[{"given":"Can","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"},{"name":"Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"},{"name":"Department of Orthopedics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"},{"name":"Department of Immunology, University of Pittsburgh, PA, 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"},{"name":"Department of Orthopedics, Xiangya Hospital, Zhongnan University, Changsha, Hunan, 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"},{"name":"Center for Pulmonary Vascular Biology and Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"You","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengwen","family":"Li","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"2021070819141461200_ref1","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":"2021070819141461200_ref2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0092-8674(88)90065-7","article-title":"Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface","volume":"54","author":"Bonilla","year":"1988","journal-title":"Cell"},{"key":"2021070819141461200_ref3","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1006\/bbrc.1993.1500","article-title":"Interaction of dystrophin with cytoskeletal proteins: binding to talin and actin","volume":"192","author":"Senter","year":"1993","journal-title":"Biochem. 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