دورية أكاديمية
أعرض في EDS

Inhibition of Mammalian Target of Rapamycin Signaling with Rapamycin Prevents Trauma-Induced Heterotopic Ossification.

التفاصيل البيبلوغرافية
العنوان: Inhibition of Mammalian Target of Rapamycin Signaling with Rapamycin Prevents Trauma-Induced Heterotopic Ossification.
المؤلفون: Qureshi AT; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland., Dey D; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland., Sanders EM; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland., Seavey JG; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, Maryland., Tomasino AM; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland., Moss K; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland., Wheatley B; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, Maryland., Cholok D; Department of Surgery, University of Michigan Health Systems, Ann Arbor, Michigan., Loder S; Department of Surgery, University of Michigan Health Systems, Ann Arbor, Michigan., Li J; Department of Surgery, University of Michigan Health Systems, Ann Arbor, Michigan., Levi B; Department of Surgery, University of Michigan Health Systems, Ann Arbor, Michigan., Davis TA; Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, Maryland. Electronic address: thomas.davis@usuhs.edu.
المصدر: The American journal of pathology [Am J Pathol] 2017 Nov; Vol. 187 (11), pp. 2536-2545. Date of Electronic Publication: 2017 Oct 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0370502 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-2191 (Electronic) Linking ISSN: 00029440 NLM ISO Abbreviation: Am J Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2011-: New York : Elsevier
Original Publication: Philadelphia [etc.] American Assn. of Pathologists [etc.]
مواضيع طبية MeSH: Bone and Bones/*drug effects , Ossification, Heterotopic/*prevention & control , Osteogenesis/*drug effects , Sirolimus/*pharmacology , TOR Serine-Threonine Kinases/*antagonists & inhibitors, Animals ; Blast Injuries/complications ; Bone and Bones/pathology ; Disease Models, Animal ; Male ; Ossification, Heterotopic/pathology ; Osteogenesis/genetics ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism ; X-Ray Microtomography/methods
مستخلص: A pressing clinical need exists for 63% to 65% of combat-wounded service members and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast-related extremity injury and traumatic injuries, respectively. The mammalian target of rapamycin pathway is a central cellular sensor of injury. We evaluated the prophylactic effects of rapamycin, a selective inhibitor of mammalian target of rapamycin signaling, on HO formation in a rat model of blast-related, polytraumatic extremity injury. Rapamycin was administered intraperitoneally daily for 14 days at 0.5 mg/kg or 2.5 mg/kg. Ectopic bone formation was monitored by micro-computed tomography and confirmed by histologic examination. Connective tissue progenitor cells, platelet-derived growth factor receptor-α-positive cells, and α-smooth muscle actin-positive blood vessels were assayed at postoperative day 7 by colony formation and immunofluorescence. Early gene expression changes were determined by low-density microarray. There was significant attenuation of 1) total new bone and soft tissue ectopic bone with 0.5 mg/kg (38.5% and 14.7%) and 2.5 mg/kg rapamycin (90.3% and 82.9%), respectively, 2) connective tissue progenitor cells, 3) platelet-derived growth factor receptor-α-positive cells, 4) α-smooth muscle actin-positive blood vessels, and 5) of key extracellular matrix remodeling (CD44, Col1a1, integrins), osteogenesis (Sp7, Runx2, Bmp2), inflammation (Cxcl5, 10, IL6, Ccl2), and angiogenesis (Angpt2) genes. No wound healing complications were noted. Our data demonstrate the efficacy of rapamycin in inhibiting blast trauma-induced HO by a multipronged mechanism.
(Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: K08 GM109105 United States GM NIGMS NIH HHS
المشرفين على المادة: EC 2.7.11.1 (TOR Serine-Threonine Kinases)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20171015 Date Completed: 20171128 Latest Revision: 20211204
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5809339
DOI: 10.1016/j.ajpath.2017.07.010
PMID: 29029772
قاعدة البيانات: MEDLINE
الوصف
تدمد:1525-2191
DOI:10.1016/j.ajpath.2017.07.010