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Ablation of the miRNA cluster 24 has profound effects on extracellular matrix protein abundance in cartilage

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Georgieva, VS, Etich, J, Bluhm, B, Zhu, M, Frie, C, Wilson, R ORCID: 0000-0003-0152-4394, Zauke, F, Bateman, J and Brachvogel, B 2020 , 'Ablation of the miRNA cluster 24 has profound effects on extracellular matrix protein abundance in cartilage' , International Journal of Molecular Sciences, vol. 21, no. 11 , pp. 1-16 , doi: 10.3390/ijms21114112.

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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: Article
Authors/Creators:Georgieva, VS and Etich, J and Bluhm, B and Zhu, M and Frie, C and Wilson, R and Zauke, F and Bateman, J and Brachvogel, B
Keywords: extracellular matrix, cartilage, miRNA, proteomics, mirc24, miR-322, miR-503, cartilage, PRG4, articular, SOX9, SOX6, MMP13
Journal or Publication Title: International Journal of Molecular Sciences
Publisher: Molecular Diversity Preservation International
ISSN: 1422-0067
DOI / ID Number: 10.3390/ijms21114112
Copyright Information:

Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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