Universität zu Köln

Georgieva, Veronika S. ORCID: 0000-0002-9234-2504, Etich, Julia ORCID: 0000-0003-3238-6692, Bluhm, Bjoern, Zhu, Mengjie, Frie, Christian, Wilson, Richard ORCID: 0000-0003-0152-4394, Zaucke, Frank ORCID: 0000-0002-7680-9354, Bateman, John ORCID: 0000-0001-8542-0730 and Brachvogel, Bent (2020). Ablation of the miRNA Cluster 24 Has Profound Effects on Extracellular Matrix Protein Abundance in Cartilage. Int. J. Mol. Sci., 21 (11). BASEL: MDPI. ISSN 1422-0067

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Abstract

MicroRNAs (miRNAs) regulate cartilage differentiation and contribute to the onset and progression of joint degeneration. These small RNA molecules may affect extracellular matrix organization (ECM) in cartilage, but for only a few miRNAs has this role been defined in vivo. Previously, we showed that cartilage-specific genetic ablation of the Mirc24 cluster in mice leads to impaired cartilage development due to increased RAF/MEK/ERK pathway activation. Here, we studied the expression of the cluster in cartilage by LacZ reporter gene assays and determined its role for extracellular matrix homeostasis by proteome and immunoblot analysis. The cluster is expressed in prehypertrophic/hypertrophic chondrocytes of the growth plate and we now show that the cluster is also highly expressed in articular cartilage. Cartilage-specific loss of the cluster leads to increased proteoglycan 4 and matrix metallopeptidase 13 levels and decreased aggrecan and collagen X levels in epiphyseal cartilage. Interestingly, these changes are linked to a decrease in SRY-related HMG box-containing (SOX) transcription factors 6 and 9, which regulate ECM production in chondrocytes. Our data suggests that the Mirc24 cluster is important for ECM homoeostasis and the expression of transcriptional regulators of matrix production in cartilage.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Georgieva, Veronika S. UNSPECIFIED orcid.org/0000-0002-9234-2504 UNSPECIFIED Etich, Julia UNSPECIFIED orcid.org/0000-0003-3238-6692 UNSPECIFIED Bluhm, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhu, Mengjie UNSPECIFIED UNSPECIFIED UNSPECIFIED Frie, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilson, Richard UNSPECIFIED orcid.org/0000-0003-0152-4394 UNSPECIFIED Zaucke, Frank UNSPECIFIED orcid.org/0000-0002-7680-9354 UNSPECIFIED Bateman, John UNSPECIFIED orcid.org/0000-0001-8542-0730 UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-331461
DOI:	10.3390/ijms21114112
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	11
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OSTEOBLAST DIFFERENTIATION; EXPRESSION; PATHWAY; COLLAGEN; SOX9; OSTEOARTHRITIS; ACTIVATION Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33146