Knockdown of PDX1 enhances the osteogenic differentiation of ADSCs partly via activation of the PI3K/Akt signaling pathway

Journal of Orthopaedic Surgery and Research

Long-Kun Fan¹  Guang-Dong Chen²  Fan Liu³ 

[1] The Department of Medical Plastic Surgery, Cangzhou Central Hospital, 061000, Cangzhou, China;The Department of Orthopedics, Cangzhou Central Hospital, No. 16 Xinhua West Road, 061000, Cangzhou, China;The First Department of Anesthesiology, Cangzhou Central Hospital, 061000, Cangzhou, China;

关键词: PDX1;    Adipose derived stem cells;    Osteogenic differentiation;    Bioinformatic analysis;   

DOI  :  10.1186/s13018-021-02825-4

来源: Springer

【 摘 要 】

BackgroundOsteoporosis (OP) is a systemic bone disease manifested as low bone mass, destruction of bone microstructure, increased bone fragility and fracture risk. The purpose of this study was to explore the role and mechanism of PDX1 for osteogenic differentiation of adipose derived stem cells (ADSCs).MethodsGSE37329 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. ADSCs were incubated with normal medium, osteogenic induction medium (OIM) and OIM+si-PDX1. Then, alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the role of PDX1 for osteogenesis of ADSCs. PI3K inhibitor, LY294002 was then added to further explore the mechanism of PDX1 for osteogenic differentiation of ADSCs. Western blot assay was used to assess the osteogenic-related markers. Graphpad software was used to perform statistically analysis.ResultsA total of 285 DEGs were obtained from analysis of the dataset GSE37329, of which 145 were upregulated and 140 were downregulated genes. These differentially expressed genes mainly enriched in cell differentiation and PI3K/Akt signaling pathway. Moreover, PDX1 was decreased in osteogenic induced ADSCs. Knockdown of PDX1 significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Administration with LY294002 could partially reversed the promotion effects of si-PDX1.ConclusionIn conclusion, knockdown of PDX1 promotes osteogenic differentiation of ADSCs through the PI3K/Akt signaling pathway.

【 授权许可】

CC BY