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Biochem Biophys Res Commun. 2018 Feb 19;496(4):1095-1101. doi: 10.1016/j.bbrc.2018.01.144. Epub 2018 Feb 2.

CBFA2T2 is required for BMP-2-induced osteogenic differentiation of mesenchymal stem cells.

Author information

1
Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China.
2
Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China.
3
Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China. Electronic address: luojun.cqmu@gmail.com.

Abstract

Bone morphogenetic protein (BMP) signaling is one of the essential pathways involved in osteogenic differentiation of mesenchymal stem cells (MSCs) and regulation of bone formation. While BMP-2 has been approved for clinic use, the underlying mechanisms remain not fully understood. In this study, we found co-repressor CBFA2T2 (core-binding factor, runt domain, alpha subunit 2, translocated to, 2) expression was significantly upregulated in response to BMP-2 treatment during osteogenic differentiation of human dental pulp stem cells (hDPSCs) and mouse bone marrow stromal cells (mBMSCs). siRNA-mediated knockdown of CBFA2T2 blunted the BMP-2-induced allkaline phosphatase (ALP) activity, mineralization of extracelluar matrix (ECM), and expression of osteogenic related genes in both hDPSCs and mBMSCs. Mechanistically, knockdown of CBFA2T2 promoted expression of euchromatic histone methyltransferase 1 (EHMT1) in mBMSCs, which further led to upregulation of H3K9me2 levels at promoter of runt related transcription factor 2 (Runx2), the master regulator of osteogenesis. Collectively, our findings indicate that CBFA2T2 is required for BMP-2-induced osteogenic differentiation of MSCs through inhibition of EHMT1-mediated histone methylation at Runx2 promoter.

KEYWORDS:

BMP signaling; CBFA2T2; EHMT1; Epigenetic regulation; Osteogenesis

PMID:
29378183
DOI:
10.1016/j.bbrc.2018.01.144
[Indexed for MEDLINE]

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