Circ_0000888 regulates osteogenic differentiation of periosteal mesenchymal stem cells in congenital pseudarthrosis of the tibia

Zhuoyang Li; Yaoxi Liu; Yiyong Huang; Qian Tan; Haibo Mei; Guanghui Zhu; Kun Liu; Ge Yang

doi:10.1016/j.isci.2023.107923

Circ_0000888 regulates osteogenic differentiation of periosteal mesenchymal stem cells in congenital pseudarthrosis of the tibia

iScience. 2023 Sep 14;26(10):107923. doi: 10.1016/j.isci.2023.107923. eCollection 2023 Oct 20.

Authors

Zhuoyang Li^{1

2}, Yaoxi Liu¹, Yiyong Huang¹, Qian Tan¹, Haibo Mei¹, Guanghui Zhu¹, Kun Liu¹, Ge Yang¹

Affiliations

¹ Department of Orthopedics, Hunan Provincial Key Laboratory of Pediatric Orthopedics, Hunan Children's Hospital, Changsha, Hunan, China.
² Department of Orthopedics, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Abstract

Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.

Keywords: Cell biology; Molecular biology; Pathophysiology; Stem cells research.