Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis

Stem Cell Research & Therapy

Hengwei Zhang¹  Yongchu Pan²  Yifei Du²  Yuli Wang²  Weina Zhou²  Fengyi Lv²  Xuan Li²  Lintong Huang²  Ruixia Wang²  Bing Li² 

[1] Department of Pathology and Laboratory Medicine and Center for Musculoskeletal Research, University of Rochester Medical Center;Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University;

关键词: Adenomatous polyposis coli;    β-Catenin;    Human amnion-derived mesenchymal stem cells;    Human bone marrow mesenchymal stem cells;    Lipopolysaccharide;    Long noncoding RNA ANRIL;   

DOI  :  10.1186/s13287-020-02105-8

来源: DOAJ

【 摘 要 】

Abstract Background and aim Periodontitis is a chronic inflammatory disease inducing the absorption of alveolar bone and leading to tooth loss. Human amnion-derived mesenchymal stem cells (HAMSCs) have been used for studying inflammatory processes. This study aimed to explore the role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) in HAMSC-driven osteogenesis in lipopolysaccharide (LPS)-induced human bone marrow mesenchymal stem cells (HBMSCs). Methods The cells were incubated with a co-culture system. Reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were used to detect the oxidative stress level. Flow cytometry was performed to determine cell proliferation. The alkaline phosphatase (ALP) activity, Alizarin red assay, cell transfection, and rat mandibular defect model were used to evaluate the osteogenic differentiation. Quantitative real-time reverse transcription–polymerase chain reaction (RT-PCR), Western blot analysis, dual-luciferase reporter assay, and immunofluorescence staining were used to evaluate the molecular mechanisms. Results This study showed that HAMSCs promoted the osteogenesis of LPS-induced HBMSCs, while the ANRIL level in HBMSCs decreased during co-culture. ANRIL had no significant influence on the proliferation of LPS-induced HBMSCs. However, its overexpression inhibited the HAMSC-driven osteogenesis in vivo and in vitro, whereas its knockdown reversed these effects. Mechanistically, this study found that downregulating ANRIL led to the overexpression of microRNA-125a (miR-125a), and further contributed to the competitive binding of miR-125a and adenomatous polyposis coli (APC), thus significantly activating the Wnt/β-catenin pathway. Conclusion The study indicated that HAMSCs promoted the osteogenic differentiation of LPS-induced HBMSCs via the ANRIL/miR-125a/APC axis, and offered a novel approach for periodontitis therapy.

【 授权许可】

Unknown