Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Bluhm, Bjorn UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehlen, Harald W. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holzer, Tatjana UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgieva, Veronika S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilig, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Pitzler, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Etich, Julia UNSPECIFIED orcid.org/0000-0003-3238-6692 UNSPECIFIED Bortecen, Toman UNSPECIFIED UNSPECIFIED UNSPECIFIED Frie, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Probst, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Belluoccio, Daniele UNSPECIFIED UNSPECIFIED UNSPECIFIED Van den Bergen, Jocelyn UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED orcid.org/0000-0002-3923-0554 UNSPECIFIED
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:	Keywords Language CHONDROCYTE PROLIFERATION; ABLATION; COLLAGEN; CELLS Multiple languages Developmental Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21532