WISP2 downregulation inhibits the osteogenic differentiation of BMSCs in congenital scoliosis by regulating Wnt/β-catenin pathway

Yang Zheng; Panyang Shen; Mengsha Tong; Hangchao Li; Conglin Ren; Fengqing Wu; Hanyu Li; Huan Yang; Bingbing Cai; Weibin Du; Xing Zhao; Shasha Yao; Renfu Quan

doi:10.1016/j.bbadis.2023.166783

WISP2 downregulation inhibits the osteogenic differentiation of BMSCs in congenital scoliosis by regulating Wnt/β-catenin pathway

Biochim Biophys Acta Mol Basis Dis. 2023 Oct;1869(7):166783. doi: 10.1016/j.bbadis.2023.166783. Epub 2023 Jun 9.

Authors

Yang Zheng¹, Panyang Shen², Mengsha Tong³, Hangchao Li³, Conglin Ren³, Fengqing Wu³, Hanyu Li³, Huan Yang⁴, Bingbing Cai⁵, Weibin Du⁵, Xing Zhao⁶, Shasha Yao⁷, Renfu Quan⁸

Affiliations

¹ Zhejiang Chinese Medical University, Hangzhou, China; Department of Orthopedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Orthopedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, China.
⁶ Department of Orthopedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: zhaox@zju.edu.cn.
⁷ Department of Orthopedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: yaoshasha@zju.edu.cn.
⁸ Zhejiang Chinese Medical University, Hangzhou, China; Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, China; Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: quanrenfu@zcmu.edu.cn.

PMID: 37302424
DOI: 10.1016/j.bbadis.2023.166783

Abstract

Objectives: Bone marrow mesenchymal stem cells (BMSCs) are instrumental in bone development, metabolism, and marrow microenvironment homeostasis. Despite this, the relevant effects and mechanisms of BMSCs on congenital scoliosis (CS) remain undefined. Herein, it becomes our focus to reveal the corresponding effects and mechanisms implicated.

Methods: BMSCs from CS patients (hereafter referred as CS-BMSCs) and healthy donors (NC-BMSCs) were observed and identified. Differentially expressed genes in BMSCs were analyzed utilizing scRNA-seq and RNA-seq profiles. The multi-differentiation potential of BMSCs following the transfection or infection was evaluated. The expression levels of factors related to osteogenic differentiation and Wnt/β-catenin pathway were further determined as appropriate.

Results: A decreased osteogenic differentiation ability was shown in CS-BMSCs. Both the proportion of LEPR⁺ BMSCs and the expression level of WNT1-inducible-signaling pathway protein 2 (WISP2) were decreased in CS-BMSCs. WISP2 knockdown suppressed the osteogenic differentiation of NC-BMSCs, while WISP2 overexpression facilitated the osteogenesis of CS-BMSCs via acting on the Wnt/β-catenin pathway.

Conclusions: Our study collectively indicates WISP2 knockdown blocks the osteogenic differentiation of BMSCs in CS by regulating Wnt/β-catenin signaling, thus providing new insights into the aetiology of CS.

Keywords: Bone marrow mesenchymal stem cells; Congenital scoliosis; WISP2; Wnt/β-catenin signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / genetics
Down-Regulation
Humans
Mesenchymal Stem Cells* / metabolism
Osteogenesis / genetics
Scoliosis* / genetics
Scoliosis* / metabolism
beta Catenin / metabolism

Substances

beta Catenin
CCN5 protein, human