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Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone-Marrow Stromal Cells in Fibrous Dysplasia.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI
    • الموضوع:
    • نبذة مختصرة :
      Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gα s and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gα s activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gα s activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gα s activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
    • Comments:
      Update of: bioRxiv. 2024 Feb 28;:. (PMID: 38529507)
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    • Grant Information:
      R01 DC000086 United States DC NIDCD NIH HHS; ZIC DC000086 United States ImNIH Intramural NIH HHS; ZIA DE000649 25 United States NH NIH HHS; Z01 DE000649 United States ImNIH Intramural NIH HHS; ZIA DE000649 United States ImNIH Intramural NIH HHS; ZIG DE000740 United States ImNIH Intramural NIH HHS
    • Contributed Indexing:
      Keywords: bone-marrow stromal cell; cytokines; fibrous dysplasia; osteoclast; osteoprogenitor; skeletal stem cell; skeleton
    • الرقم المعرف:
      0 (Cytokines)
      EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
    • الموضوع:
      Date Created: 20240510 Date Completed: 20240510 Latest Revision: 20240520
    • الموضوع:
      20240520
    • الرقم المعرف:
      PMC11083355
    • الرقم المعرف:
      10.3390/cells13090774
    • الرقم المعرف:
      38727310