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2015-01-05

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cc-by (c) Rica, Lorenzo de la et al., 2015
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/105828

NF-κB-direct activation of microRNAs with repressive effects on monocyte-specific genes is critical for osteoclast differentiation

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https://doi.org/10.1186/s13059-014-0561-5

Abstract

Monocyte-to-osteoclast conversion is a unique terminal differentiation process that is exacerbated in rheumatoid arthritis and bone metastasis. The mechanisms implicated in upregulating osteoclast-specific genes involve transcription factors, epigenetic regulators and microRNAs (miRNAs). It is less well known how downregulation of osteoclast-inappropriate genes is achieved. RESULTS: In this study, analysis of miRNA expression changes in osteoclast differentiation from human primary monocytes revealed the rapid upregulation of two miRNA clusters, miR-212/132 and miR-99b/let-7e/125a. We demonstrate that they negatively target monocyte-specific and immunomodulatory genes like TNFAIP3, IGF1R and IL15. Depletion of these miRNAs inhibits osteoclast differentiation and upregulates their targets. These miRNAs are also upregulated in other inflammatory monocytic differentiation processes. Most importantly, we demonstrate for the first time the direct involvement of Nuclear Factor kappa B (NF-κB) in the regulation of these miRNAs, as well as with their targets, whereby NF-κB p65 binds the promoters of these two miRNA clusters and NF-κB inhibition or depletion results in impaired upregulation of their expression. CONCLUSIONS:Our results reveal the direct involvement of NF-κB in shutting down certain monocyte-specific genes, including some anti-inflammatory activities, through a miRNA-dependent mechanism for proper osteoclast differentiation.

Subject

Micro RNAs, Genètica mèdica, Diferenciació cel·lular, Artritis reumatoide, Metàstasi, Càncer d'ossos

Subject (English)

MicroRNAs, Medical genetics, Cell diferentiation, Rheumatoid arthritis, Metastasis, Bones cancer

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Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Publicacions de projectes de recerca finançats per la UE

Citation

RICA LÁZARO, Lorenzo de la, et al. NF-κB-direct activation of microRNAs with repressive effects on monocyte-specific genes is critical for osteoclast differentiation. Genome Biology. 2015. Vol. 16, num. 2, pags. 1-17. ISSN 1465-6906. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/105828

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