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:
CreatorsEmailORCIDORCID Put Code
Georgieva, Veronika S.UNSPECIFIEDorcid.org/0000-0002-9234-2504UNSPECIFIED
Etich, JuliaUNSPECIFIEDorcid.org/0000-0003-3238-6692UNSPECIFIED
Bluhm, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, MengjieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frie, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilson, RichardUNSPECIFIEDorcid.org/0000-0003-0152-4394UNSPECIFIED
Zaucke, FrankUNSPECIFIEDorcid.org/0000-0002-7680-9354UNSPECIFIED
Bateman, JohnUNSPECIFIEDorcid.org/0000-0001-8542-0730UNSPECIFIED
Brachvogel, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
OSTEOBLAST DIFFERENTIATION; EXPRESSION; PATHWAY; COLLAGEN; SOX9; OSTEOARTHRITIS; ACTIVATIONMultiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33146

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