Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging
Chang-Jun Li, … , Yan Huang, Xiang-Hang Luo
Chang-Jun Li, … , Yan Huang, Xiang-Hang Luo
Published December 3, 2018; First published October 22, 2018
Citation Information: J Clin Invest. 2018;128(12):5251-5266. https://doi.org/10.1172/JCI99044.
View: Text | PDF
Categories: Research Article Endocrinology

Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging

  • Text
  • PDF
Abstract

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs.

Authors

Chang-Jun Li, Ye Xiao, Mi Yang, Tian Su, Xi Sun, Qi Guo, Yan Huang, Xiang-Hang Luo

×

Figure 1

Bmncr expression in BMSCs decreased during aging.

Options: View larger image (or click on image) Download as PowerPoint

Bmncr expression in BMSCs decreased during aging.
(A) Heat map of micro...
(A) Heat map of microarray profiling results of deregulated lncRNAs in BMSCs from young and aged mice (fold change > 3, false-discovery rate < 0.20). Red arrow indicates the lncRNA (Bmncr) selected for study. (B) qRT-PCR analysis of the levels of Bmncr expression in BMSCs derived from the mice at different ages (n = 5 per group). (C and D) Age-associated changes of BMNCR levels in human BMSCs from 32 males (C) and 32 females (D). Data are mean ± SD. *P < 0.01 (1-way ANOVA).
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts