![]() ![]() Osteoclast differentiation is an intricate process, regulated at multiple levels by transcription factors and post-translational modifications. The maintenance of bone homeostasis requires a tight control of the number and activity of osteoblasts, the bone-forming cells, and osteoclasts, the only cells able to resorb mineralized bone matrix. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIAMS or the NIH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This project was supported by Grant Number AR044877 (to AMD) and AR055143 (to SKL) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health. Received: DecemAccepted: AugPublished: September 15, 2014Ĭopyright: © 2014 Franceschetti et al. This novel data set contributes to our understanding of the molecular mechanisms regulating the complex process of osteoclast differentiation.Ĭitation: Franceschetti T, Dole NS, Kessler CB, Lee S-K, Delany AM (2014) Pathway Analysis of MicroRNA Expression Profile during Murine Osteoclastogenesis. Overall, our study is unique in that we identified miRNAs differentially expressed during early, mid, and late osteoclastogenesis in a population of primary mouse bone marrow cells enriched for osteoclast progenitors. ![]() This suggests that many miRNA clusters differentially expressed during osteoclastogenesis converge on some key functional pathways. Computational analyses predicted mTOR, PI3 kinase/AKT, cell-matrix interactions, actin cytoskeleton organization, focal adhesion, and axon guidance pathways to be top targets of several miRNA clusters. In contrast, overexpression of miR-451 had no effect. Inhibition of miR-365 increased osteoclast number but decreased osteoclast size, while miR-99b inhibition decreased both osteoclast number and size. We validated the function and expression of miR-365, miR-451, and miR-99b, which were found in distinct clusters. Expression of 93 miRNAs, changed by >2 fold during early, mid, and late stages of osteoclastogenesis, were identified and sorted into 7 clusters. An Agilent microarray platform was used to analyze expression of mature miRNAs in an enriched population of murine bone marrow osteoclast precursors (depleted of B220 + and CD3 + cells) undergoing 1, 3, or 5 days of RANKL-driven differentiation. However, a more complete miRNA signature, encompassing early, mid and late stages of osteoclastogenesis, is wanting. Prior studies profiled miRNA expression in murine osteoclast precursors treated with RANKL for 24 hours. Disruption of miRNA-mediated regulation alters osteoclast formation and bone resorption. ![]() microRNAs (miRNAs) are key post-transcriptional regulators that repress expression of target mRNAs controlling osteoclast proliferation, differentiation, and apoptosis. This stringent regulation is crucial to prevent excessive or insufficient bone resorption and to maintain bone homeostasis. ![]() Osteoclast formation and function are tightly regulated by transcriptional, post-transcriptional and post-translational mechanisms. To design novel therapeutics against bone loss, understanding the molecular mechanisms regulating osteoclastogenesis is critical. ![]()
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