Bluhm, Bjorn, Ehlen, Harald W. A., Holzer, Tatjana, Georgieva, Veronika S., Heilig, Juliane, Pitzler, Lena, Etich, Julia ORCID: 0000-0003-3238-6692, Bortecen, Toman, Frie, Christian, Probst, Kristina, Niehoff, Anja, Belluoccio, Daniele, Van den Bergen, Jocelyn and Brachvogel, Bent ORCID: 0000-0002-3923-0554 (2017). miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage. Development, 144 (19). S. 3562 - 3578. CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9129

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Abstract

Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development. Here, we characterize a miRNA that promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway, only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1 mRNA to raise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation of miR322 in mice linked the loss of miR-322 to decreased MEK1 levels and to increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure. Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bluhm, BjornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehlen, Harald W. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holzer, TatjanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Georgieva, Veronika S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heilig, JulianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pitzler, LenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Etich, JuliaUNSPECIFIEDorcid.org/0000-0003-3238-6692UNSPECIFIED
Bortecen, TomanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frie, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Probst, KristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niehoff, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belluoccio, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van den Bergen, JocelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brachvogel, BentUNSPECIFIEDorcid.org/0000-0002-3923-0554UNSPECIFIED
URN: urn:nbn:de:hbz:38-215325
DOI: 10.1242/dev.148429
Journal or Publication Title: Development
Volume: 144
Number: 19
Page Range: S. 3562 - 3578
Date: 2017
Publisher: COMPANY BIOLOGISTS LTD
Place of Publication: CAMBRIDGE
ISSN: 1477-9129
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHONDROCYTE PROLIFERATION; ABLATION; COLLAGEN; CELLSMultiple languages
Developmental BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21532

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