DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes

Abstract The Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. Matrix metalloproteinase (MMP)-13 is a major contributor to cartilage degradation in osteoarthritis (OA). We and others have shown that the abnormal MMP13 gene expression in OA...

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Autores principales:	Atsushi Takahashi, María C. de Andrés, Ko Hashimoto, Eiji Itoi, Miguel Otero, Mary B. Goldring, Richard O. C. Oreffo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd76ae98337946548bf91121591784a3
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spelling	oai:doaj.org-article:cd76ae98337946548bf91121591784a32021-12-02T12:32:01ZDNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes10.1038/s41598-017-08418-82045-2322https://doaj.org/article/cd76ae98337946548bf91121591784a32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08418-8https://doaj.org/toc/2045-2322Abstract The Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. Matrix metalloproteinase (MMP)-13 is a major contributor to cartilage degradation in osteoarthritis (OA). We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA methylation status of specific CpG sites of the proximal promoter, as well as by the actions of different transactivators, including RUNX2. The present study aimed to determine the influence of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes. We observed a significant correlation between MMP13 mRNA levels and RUNX2 gene expression in human OA chondrocytes. RUNX2 overexpression enhanced MMP13 promoter activity, independent of the MMP13 promoter methylation status. A significant negative correlation was observed between RUNX2 mRNA levels in OA chondrocytes and the percentage methylation of the CpG sites in the RUNX2 P1 promoter. Accordingly, the activity of the wild type RUNX2 promoter was decreased upon methylation treatment in vitro. We conclude that RUNX2 gene transcription is regulated by the methylation status of specific CpG sites in the promoter and may determine RUNX2 availability in OA cartilage for transactivation of genes such as MMP13.Atsushi TakahashiMaría C. de AndrésKo HashimotoEiji ItoiMiguel OteroMary B. GoldringRichard O. C. OreffoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atsushi Takahashi María C. de Andrés Ko Hashimoto Eiji Itoi Miguel Otero Mary B. Goldring Richard O. C. Oreffo DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
description	Abstract The Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. Matrix metalloproteinase (MMP)-13 is a major contributor to cartilage degradation in osteoarthritis (OA). We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA methylation status of specific CpG sites of the proximal promoter, as well as by the actions of different transactivators, including RUNX2. The present study aimed to determine the influence of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes. We observed a significant correlation between MMP13 mRNA levels and RUNX2 gene expression in human OA chondrocytes. RUNX2 overexpression enhanced MMP13 promoter activity, independent of the MMP13 promoter methylation status. A significant negative correlation was observed between RUNX2 mRNA levels in OA chondrocytes and the percentage methylation of the CpG sites in the RUNX2 P1 promoter. Accordingly, the activity of the wild type RUNX2 promoter was decreased upon methylation treatment in vitro. We conclude that RUNX2 gene transcription is regulated by the methylation status of specific CpG sites in the promoter and may determine RUNX2 availability in OA cartilage for transactivation of genes such as MMP13.
format	article
author	Atsushi Takahashi María C. de Andrés Ko Hashimoto Eiji Itoi Miguel Otero Mary B. Goldring Richard O. C. Oreffo
author_facet	Atsushi Takahashi María C. de Andrés Ko Hashimoto Eiji Itoi Miguel Otero Mary B. Goldring Richard O. C. Oreffo
author_sort	Atsushi Takahashi
title	DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
title_short	DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
title_full	DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
title_fullStr	DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
title_full_unstemmed	DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
title_sort	dna methylation of the runx2 p1 promoter mediates mmp13 transcription in chondrocytes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cd76ae98337946548bf91121591784a3
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DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes

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