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Lookup NU author(s): Dan Hayman, Dr Francesca Johnson de Sousa Brito, Hua LinORCiD, Yao Hao, Rachel Pearson, Dr Jamie Soul, Dr Katarzyna PirogORCiD, Dr Matthew Barter, Professor David YoungORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s). MicroRNAs (miRNAs) modulate the expression of other RNA molecules. One miRNA can target many transcripts, allowing each miRNA to play key roles in many biological pathways. Defects in bone homeostasis result in common age-related diseases including osteoporosis. Serum levels of miR-324-3p positively correlate with several features of bone maintenance. In contrast here, using in vivo micro-computed tomography and histology, global miR-324-null mice demonstrated increased bone mineral density and both trabecular and cortical thickness, with effect magnitudes increasing with age. The bone marrow of miR-324-null mice had reduced lipid content while TRAP staining revealed a decrease in osteoclasts, with histomorphometry demonstrating an increased rate of bone formation. Ex vivo assays showed that the high bone mass phenotype of miR-324-null mice resulted from both increased osteoblast activity and decreased osteoclastogenesis. RNA-seq analysis of osteoblasts, osteoclasts and bone marrow macrophages and target validation assays identified that the osteoclast fusion regulator Pin1 and the master osteogenic regulator Runx2 were targets of miR-324-5p in osteoclast lineage cells and osteoblasts, respectively. Indeed, in vitro Runx2 overexpression recapitulated the increased osteogenesis and decreased adipogenesis phenotype observed in vivo by the loss of miR-324. Overall, these data demonstrate the importance of miR-324 in bone homeostasis by regulating aspects of both bone formation and remodelling. Elucidation of pathways regulated by miR-324 offer promise for the treatment of bone diseases such as osteoporosis.
Author(s): Hayman DJ, Johnson de Sousa Brito FM, Lin H, Prior A, Charlesworth G, Hao Y, Pearson RD, Soul J, Clark IM, Pirog KA, Barter MJ, van't Hof RJ, Young DA
Publication type: Article
Publication status: Published
Journal: Bone
Year: 2025
Volume: 190
Print publication date: 01/01/2025
Online publication date: 09/10/2024
Acceptance date: 03/10/2024
Date deposited: 21/10/2024
ISSN (electronic): 1873-2763
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.bone.2024.117273
DOI: 10.1016/j.bone.2024.117273
Data Access Statement: Data will be made available on request.
PubMed id: 39383985
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