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

Citation

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, Ablation of the miRNA cluster 24 has profound effects on extracellular matrix protein abundance in cartilage, International Journal of Molecular Sciences, 21, (11) Article 4112. ISSN 1422-0067 (2020) [Refereed Article]


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

DOI: doi:10.3390/ijms21114112

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 Details

Item Type:Refereed Article
Keywords:extracellular matrix, cartilage, miRNA, proteomics, mirc24, miR-322, miR-503, cartilage, PRG4, articular, SOX9, SOX6, MMP13
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Proteomics and Intermolecular Interactions (excl. Medical Proteomics)
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
UTAS Author:Wilson, R (Dr Richard Wilson)
ID Code:139332
Year Published:2020
Deposited By:Central Science Laboratory
Deposited On:2020-06-10
Last Modified:2020-07-27
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