MiR-143-3p Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Targeting KLF5 and Inactivating the Wnt/β-Catenin Pathway

Kaixin Wangzhou; Zhiying Lai; Zishao Lu; Wanren Fu; Cheng Liu; Zhengeng Liang; Yi Tan; Conghui Li; Chunbo Hao

doi:10.3389/fphys.2020.606967

MiR-143-3p Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Targeting KLF5 and Inactivating the Wnt/β-Catenin Pathway

Front Physiol. 2021 Feb 2:11:606967. doi: 10.3389/fphys.2020.606967. eCollection 2020.

Authors

Kaixin Wangzhou¹, Zhiying Lai², Zishao Lu², Wanren Fu², Cheng Liu³, Zhengeng Liang⁴, Yi Tan⁴, Conghui Li⁴, Chunbo Hao⁴

Affiliations

¹ School of Management, Hainan Medical University, Haikou, China.
² College of Stomatology, Hainan Medical University, Haikou, China.
³ Department of Stomatology, Harbin Stomatological Hospital, Harbin, China.
⁴ Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.

Abstract

Human periodontal ligament cells (hPDLCs) play a vital role in cell regeneration and tissue repair with multi-directional differentiation potential. microRNAs (miRs) are implicated in the osteogenesis of hPDLCs. This study explored the mechanism of miR-143-3p in osteogenesis of hPDLCs. Osteogenic differentiation of isolated hPDLCs was induced. KLF5 expression during osteogenic differentiation of hPDLCs was detected and then silenced in hPDLCs. Binding relationship between KLF5 and miR-143-3p was predicted and verified. hPDLCs were treated with miR-143-3p mimic or overexpressing KLF5, and then osteogenic specific markers and mineralized nodules were measured. The key factors of the Wnt/β-catenin pathway during osteogenesis of hPDLCs were measured. KLF5 expression was upregulated during osteogenesis of hPDLCs. KLF5 silencing or miR-143-3p mimic reduced osteogenic specific markers and mineralized nodules. Overexpression of KLF5 could reverse the inhibitory effect of miR-143-3p on osteogenic differentiation. miR-143-3p mimic and KLF5 silencing inactivated the Wnt/β-catenin pathway. Activation of the Wnt/β-catenin pathway reversed the repression effect of miR-143-3p mimic on osteogenesis of hPDLCs. In conclusion, miR-143-3p inhibited osteogenic differentiation of hPDLCs by targeting KLF5 and inactivating the Wnt/β-catenin pathway.

Keywords: KLF5; Wnt/β-catenin pathway; human periodontal ligament cells; microRNA-143-3p; osteogenic differentiation.