MicroRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling

  1. Shumin Wang
  2. Eri O Maruyama
  3. John Martinez
  4. Justin Lopes
  5. Trunee Hsu
  6. Wencheng Wu
  7. Wei Hsu  Is a corresponding author
  8. Takamitsu Maruyama  Is a corresponding author
  1. University of Rochester Medical Center, United States
  2. The Forsyth Institute, United States
  3. Case Western Reserve University, United States
  4. Harvard University, United States

Abstract

The ability to simultaneously modulate a set of genes for lineage-specific development has made microRNA an ideal master regulator for organogenesis. However, most microRNA deletions do not exhibit obvious phenotypic defects possibly due to functional redundancy. MicroRNAs are known to regulate skeletal lineages as the loss of their maturation enzyme Dicer impairs bone remodeling processes. Therefore, it is important to identify specific microRNA essential for bone homeostasis. We report the loss of MIR27a causing severe osteoporosis in mice. MIR27a affects osteoclast-mediated bone resorption but not osteoblast-mediated bone formation during skeletal remodeling. Gene profiling and bioinformatics further identify the specific targets of MIR27a in osteoclast cells. MIR27a exerts its effects on osteoclast differentiation through modulation of Squstm1/p62 whose mutations have been linked to Paget's disease of bone. Our findings reveal a new MIR27a-p62 axis necessary and sufficient to mediate osteoclast differentiation and highlight a therapeutic implication for osteoporosis.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file.

Article and author information

Author details

  1. Shumin Wang

    University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0217-6600
  2. Eri O Maruyama

    The Forsyth Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. John Martinez

    University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0040-8519
  4. Justin Lopes

    The Forsyth Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Trunee Hsu

    Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Wencheng Wu

    University of Rochester Medical Center, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Wei Hsu

    Harvard University, Cambridge, United States
    For correspondence
    wei.hsu@hsdm.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6738-6030
  8. Takamitsu Maruyama

    The Forsyth Institute, Cambridge, United States
    For correspondence
    tmaruyama@forsyth.org
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (DE015654)

  • Wei Hsu

National Institutes of Health (DE026936)

  • Wei Hsu

National Institutes of Health (DE028696)

  • Takamitsu Maruyama

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ritu Trivedi, CSIR-Central Drug Research Institute, India

Ethics

Animal experimentation: Care and use of experimental animals described in this work comply with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#102402) of the University of Rochester and protocols (#21-005) of the Forsyth Institute.

Version history

  1. Received: April 26, 2022
  2. Preprint posted: June 17, 2022 (view preprint)
  3. Accepted: February 7, 2023
  4. Accepted Manuscript published: February 8, 2023 (version 1)
  5. Version of Record published: February 22, 2023 (version 2)

Copyright

© 2023, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shumin Wang
  2. Eri O Maruyama
  3. John Martinez
  4. Justin Lopes
  5. Trunee Hsu
  6. Wencheng Wu
  7. Wei Hsu
  8. Takamitsu Maruyama
(2023)
MicroRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling
eLife 12:e79768.
https://doi.org/10.7554/eLife.79768

Share this article

https://doi.org/10.7554/eLife.79768

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