دورية أكاديمية
أعرض في EDS

The Osteocyte Transcriptome Is Extensively Dysregulated in Mouse Models of Osteogenesis Imperfecta.

التفاصيل البيبلوغرافية
العنوان: The Osteocyte Transcriptome Is Extensively Dysregulated in Mouse Models of Osteogenesis Imperfecta.
المؤلفون: Zimmerman SM; Department of Physiology and Biophysics University of Arkansas for Medical Sciences Little Rock AR USA., Dimori M; Department of Physiology and Biophysics University of Arkansas for Medical Sciences Little Rock AR USA., Heard-Lipsmeyer ME; Department of Physiology and Biophysics University of Arkansas for Medical Sciences Little Rock AR USA., Morello R; Department of Physiology and Biophysics University of Arkansas for Medical Sciences Little Rock AR USA.; Department of Orthopaedic Surgery University of Arkansas for Medical Sciences Little Rock AR USA.; Division of Genetics University of Arkansas for Medical Sciences Little Rock AR USA.
المصدر: JBMR plus [JBMR Plus] 2019 Feb 11; Vol. 3 (7), pp. e10171. Date of Electronic Publication: 2019 Feb 11 (Print Publication: 2019).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101707013 Publication Model: eCollection Cited Medium: Internet ISSN: 2473-4039 (Electronic) Linking ISSN: 24734039 NLM ISO Abbreviation: JBMR Plus Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2024- : Oxford : Oxford University Press
Original Publication: [Chichester, West Sussex, UK] : John Wiley & Sons, [2017]-
مستخلص: Osteocytes are long-lived, highly interconnected, terminally differentiated osteoblasts that reside within mineralized bone matrix. They constitute about 95% of adult bone cells and play important functions including in the regulation of bone remodeling, phosphate homeostasis, and mechanical stimuli sensing and response. However, the role of osteocytes in the pathogenesis of congenital diseases of abnormal bone matrix is poorly understood. This study characterized in vivo transcriptional changes in osteocytes from Crtap KO and oim/oim mouse models of osteogenesis imperfecta (OI) compared with wild-type (WT) control mice. To do this, RNA was extracted from osteocyte-enriched cortical femurs and tibias, sequenced and subsequently analyzed to identify differentially expressed transcripts. These models were chosen because they mimic two types of OI with different genetic mutations that result in distinct type I collagen defects. A large number of transcripts were dysregulated in either model of OI, but 281 of them were similarly up- or downregulated in both compared with WT controls. Conversely, very few transcripts were differentially expressed between the Crtap KO and oim/oim mice, indicating that distinct alterations in type I collagen can lead to shared pathogenic processes and similar phenotypic outcomes. Bioinformatics analyses identified several critical hubs of dysregulation that were enriched in annotation terms such as development and differentiation, ECM and collagen fibril organization, cell adhesion, signaling, regulatory processes, pattern binding, chemotaxis, and cell projections. The data further indicated alterations in important signaling pathways such as WNT and TGF-β but also highlighted new candidate genes to pursue in future studies. Overall, our study suggested that the osteocyte transcriptome is broadly dysregulated in OI with potential long-term consequences at the cellular level, which deserve further investigations. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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معلومات مُعتمدة: P20 GM125503 United States GM NIGMS NIH HHS; R01 AR060823 United States AR NIAMS NIH HHS
فهرسة مساهمة: Keywords: COLLAGEN; GENETIC ANIMAL MODELS; OSTEOCYTES; OSTEOGENESIS IMPERFECTA; RNASEQ
تواريخ الأحداث: Date Created: 20190803 Latest Revision: 20201001
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6659450
DOI: 10.1002/jbm4.10171
PMID: 31372585
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-4039
DOI:10.1002/jbm4.10171