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139332 - Ablation of the miRNA cluster 24 has profound effects.pdf (1.74 MB)

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

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posted on 2023-05-20, 14:56 authored by Georgieva, VS, Etich, J, Bluhm, B, Zhu, M, Frie, C, Richard WilsonRichard Wilson, Zauke, F, Bateman, J, Brachvogel, B
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.

History

Publication title

International Journal of Molecular Sciences

Volume

21

Issue

11

Article number

4112

Number

4112

Pagination

1-16

ISSN

1422-0067

Publisher

Molecular Diversity Preservation International

Place of publication

Matthaeusstrasse 11, Basel, Switzerland, Ch-4057

Rights statement

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

Repository Status

  • Open

Socio-economic Objectives

Health related to ageing; Expanding knowledge in the health sciences

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