Mir-142-5p inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting Lhx8

Yongjun Du; Hui Zhong; Chen Yu; Yan Lv; Yueyi Yao; Zhi Peng; Sheng Lu

doi:10.1016/j.heliyon.2023.e19878

Mir-142-5p inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting Lhx8

Heliyon. 2023 Sep 9;9(9):e19878. doi: 10.1016/j.heliyon.2023.e19878. eCollection 2023 Sep.

Authors

Yongjun Du^{1

2}, Hui Zhong¹, Chen Yu¹, Yan Lv^{1

3}, Yueyi Yao⁴, Zhi Peng¹, Sheng Lu¹

Affiliations

¹ Orthopaedics Department, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, The Key Laboratory of Digital Orthopaedics of Yunnan Provincial, Yunnan Provincial Center for Clinical Medicine in Spinal and Spinal Cord Disorders, Kunming, 650034, China.
² Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
³ Faculty of Life science and Technology, Kunming University of Science and Technology, Kunming, 650500, China.
⁴ Science and Technology Achievement Incubation Center, Kunming Medical University, 1168 Chunrongxi Road, Kunming, Yunnan 650500, China.

Abstract

Osteoporosis (OP), a common systemic bone metabolism disease with a high incidence rate, is a serious health risk factor. Osteogenic differentiation balance is regulated by bone marrow mesenchymal stem cells (BMSCs) and plays a key role in OP occurrence and progression. Although, LIM homeobox 8 (Lhx8) has been identified to affect BMSCs osteogenic differentiation, its roles in OP and the associated mechanism remains unclear. Here, we aimed to elucidate the role and mechanism of Lhx8 in the osteogenic differentiation of BMSCs. BMSCs isolated from wild type and OP Sprague-Dawley rats were cultured and confirmed via flow cytometry and microscopy. Based on dual-luciferase reporter assay, BMSCs were transfected with miR-142-5p mimics and miR-NC (negative control). Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were performed to determine the role of Lhx8 in BMSCs osteogenic differentiation. Lhx8 expression was significantly reduced in OP, whereas that of miR-142-5p, a possible Lhx8 regulator, was significantly upregulated. Dual-luciferase reporter assay demonstrated that miR-142-5p exerted a direct targeted regulatory effect on Lhx8. Moreover, miR-142-5p mimics significantly inhibited BMSCs osteogenic differentiation as well as Lhx8 expression in vitro, indicating that miR-142-5p may be involved in BMSCs osteogenic differentiation via Lhx8 expression regulation and may serve as a potential diagnostic target for OP. Overall, these findings indicated that miR-142-5p inhibits BMSCs osteogenic differentiation by suppressing Lhx8. These may serve as a foundation for further studies on OP treatment based on miR-142-5p targeting.

Keywords: Bone marrow mesenchymal stem cells; Lhx8; Osteogenic differentiation; Osteoporosis; miR-142-5p.