MicroRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling
- University of Rochester Medical Center, United States
- The Forsyth Institute, United States
- Case Western Reserve University, United States
- 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.
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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.
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.
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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MicroRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling
eLife 12:e79768.
https://doi.org/10.7554/eLife.79768
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