KLF14 inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells by downregulating WNT3A

Junquan Weng; Jiahua Wu; Weixuan Chen; Haidong Fan; Huijuan Liu

KLF14 inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells by downregulating WNT3A

Am J Transl Res. 2020 Aug 15;12(8):4445-4455. eCollection 2020.

Authors

Junquan Weng¹, Jiahua Wu², Weixuan Chen¹, Haidong Fan¹, Huijuan Liu¹

Affiliations

¹ Department of Stomatology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University Guangdong, P. R. China.
² Department of Stomatology, Union Hospital of Shenzhen, Huazhong University of Science and Technology Guangdong, P. R. China.

PMID: 32913518
PMCID: PMC7476154

Abstract

KLF14 belongs to the Krüppel-like factor (KLF) family of transcription factors. The KLF family activate and/or repress transcription in a promoter- and cell-dependent manner by interacting with co-suppressors or co-activators. However, the function and mechanism of KLF14 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) is unknown. This study explores the impact and molecular mechanism of KLF14 in hMSC osteogenic differentiation in vitro. We found that KLF14 was highly expressed in hMSCs, and KLF14 expression gradually decreased after inducing osteogenic differentiation. Inhibiting KLF14 expression promoted osteogenic differentiation of hMSCs. We also found that KLF14 interacted with the WNT3A promoter. This interaction decreased expression of WNT3A and downstream osteogenesis-related target genes in the WNT signaling pathway, and resulted in cell cycle arrest. In conclusion, we describe a new mechanism for KLF14 in differentiation of hMSCs into osteoblasts and suggest a new target for clinical therapeutics related to human bone development.

Keywords: KLF14; WNT3A; hMSC; osteogenic differentiation.