دورية أكاديمية
أعرض في EDS

Peroxisome proliferator activated receptor-γ in osteoblasts controls bone formation and fat mass by regulating sclerostin expression.

التفاصيل البيبلوغرافية
العنوان: Peroxisome proliferator activated receptor-γ in osteoblasts controls bone formation and fat mass by regulating sclerostin expression.
المؤلفون: Kim SP; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Seward AH; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Garcia-Diaz J; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Alekos N; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Gould NR; Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Aja S; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Stains JP; Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Wolfgang MJ; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Riddle RC; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Research and Development Service, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
المصدر: IScience [iScience] 2023 May 29; Vol. 26 (7), pp. 106999. Date of Electronic Publication: 2023 May 29 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: The nuclear receptor peroxisome proliferator activated receptor-γ (PPARγ) is a key contributor to metabolic function via its adipogenic and insulin-sensitizing functions, but it has negative effects on skeletal homeostasis. Here, we questioned whether the skeletal and metabolic actions of PPARγ are linked. Ablating Pparg expression in osteoblasts and osteocytes produced a high bone mass phenotype, secondary to increased osteoblast activity, and a reduction in subcutaneous fat mass because of reduced fatty acid synthesis and increased fat oxidation. The skeletal and metabolic phenotypes in Pparg mutants proceed from the regulation of sclerostin production by PPARγ. Mutants exhibited reductions in skeletal Sost expression and serum sclerostin levels while increasing production normalized both phenotypes. Importantly, disrupting the production of sclerostin synergized with the insulin-sensitizing actions of a PPARγ agonist while preventing bone loss. These data suggest that modulating sclerostin action may prevent bone loss associated with anti-diabetic therapies and augment their metabolic actions.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
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معلومات مُعتمدة: I01 BX003724 United States BX BLRD VA
فهرسة مساهمة: Keywords: Cell biology; Molecular physiology
تواريخ الأحداث: Date Created: 20230803 Latest Revision: 20230805
رمز التحديث: 20230805
مُعرف محوري في PubMed: PMC10391670
DOI: 10.1016/j.isci.2023.106999
PMID: 37534168
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2023.106999