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Publication : miRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling.

First Author  Wang S Year  2023
Journal  Elife Volume  12
PubMed ID  36752600 Mgi Jnum  J:345025
Mgi Id  MGI:7579502 Doi  10.7554/eLife.79768
Citation  Wang S, et al. (2023) miRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling. Elife 12
abstractText  The ability to simultaneously modulate a set of genes for lineage-specific development has made miRNA an ideal master regulator for organogenesis. However, most miRNA deletions do not exhibit obvious phenotypic defects possibly due to functional redundancy. miRNAs 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 miRNA 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.
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