N-myc downstream regulated gene 1 suppresses osteoblast differentiation through inactivating Wnt/β-catenin signaling

Stem Cell Research & Therapy

Xiaoxia Li¹  Baoli Wang²  Lijie Tian²  Endong Zhu²  Liying Shan²  Hairui Yuan²  Xiaoli Shi³  Yunzhu Cen⁴  Ying Liu⁴ 

[1] College of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China;NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Institute of Endocrinology, Tianjin Medical University, 300134, Tianjin, China;NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Institute of Endocrinology, Tianjin Medical University, 300134, Tianjin, China;College of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China;Stomatological Hospital, Tianjin Medical University, 300070, Tianjin, China;

关键词: Adipocyte;    Differentiation;    N-myc downstream regulated gene 1;    Osteoblast;    Wnt/β-catenin;   

DOI  :  10.1186/s13287-022-02714-5

来源: Springer

【 摘 要 】

BackgroundN-myc downstream regulated gene 1 (NDRG1) plays a role in a variety of biological processes including differentiation of osteoclasts. However, it is not known if and how NDRG1 regulates osteogenic differentiation of marrow stromal progenitor cells.MethodsGene expression profiling analysis was performed to study the expression level of Ndrg1 during osteogenic and adipogenic differentiation. Gain-of-function and/or loss-of function experiments were carried out to study the role of NDRG1 in the proliferation and differentiation of marrow stromal progenitor cells and the mechanism underlying the function was investigated. Finally, in vivo transfection of Ndrg1 siRNA was done and its effect on osteogenic and adipogenic differentiation in mice was explored.ResultsGene expression profiling analysis revealed that NDRG1 level was regulated during osteogenic and adipogenic differentiation of progenitor cells. The functional experiments demonstrated that NDRG1 negatively regulated the cell growth, and reciprocally modulated the osteogenic and adipogenic commitment of marrow stromal progenitor cells, driving the cells to differentiate toward adipocytes at the expense of osteoblast differentiation. Moreover, NDRG1 interacted with low-density lipoprotein receptor-related protein 6 (LRP6) in the stromal progenitor cells and inactivated the canonical Wnt/β-catenin signaling cascade. Furthermore, the impaired differentiation of progenitor cells induced by Ndrg1 siRNA could be attenuated when β-catenin was simultaneously silenced. Finally, in vivo transfection of Ndrg1 siRNA to the marrow of mice prevented the inactivation of canonical Wnt signaling in the BMSCs of ovariectomized mice, and ameliorated the reduction of osteoblasts on the trabeculae and increase of fat accumulation in the marrow observed in the ovariectomized mice.ConclusionThis study has provided evidences that NDRG1 plays a role in reciprocally modulating osteogenic and adipogenic commitment of marrow stromal progenitor cells through inactivating canonical Wnt signaling.

【 授权许可】

CC BY