Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/β-Catenin Signaling Pathway
Autor: | Menghu Han, Yanming Cao, Xiao Wei, Weihao Zheng, Lili Zhao, Shouyu Xiang, Ram Ishwar Yadav, Yichuan Shi, Jianliang Gao |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Gene knockdown Article Subject General Immunology and Microbiology Chemistry Wnt signaling pathway General Medicine General Biochemistry Genetics and Molecular Biology RUNX2 Transplantation 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine stomatognathic system 030220 oncology & carcinogenesis Cancer research Medicine Sclerostin Signal transduction Stem cell Icariin |
Zdroj: | BioMed Research International, Vol 2021 (2021) |
ISSN: | 2314-6141 2314-6133 |
DOI: | 10.1155/2021/6666836 |
Popis: | Osteoporosis (OP) is a metabolic disease characterized by decreased bone mass and increased risk of fragility fractures, which significantly reduces the quality of life. Stem cell-based therapies, especially using bone marrow mesenchymal stem cells (BMSCs), are a promising strategy for treating OP. Nevertheless, the survival and differentiation rates of the transplanted BMSCs are low, which limits their therapeutic efficiency. Icariin (ICA) is a traditional Chinese medicine formulation that is prescribed for tonifying the kidneys. It also promotes the proliferation and osteogenic differentiation of BMSCs, although the specific mechanism remains unclear. Based on our previous research, we hypothesized that ICA promotes bone formation via the sclerostin/Wnt/β-catenin signaling pathway. We isolated rat BMSCs and transfected them with sclerostin gene (SOST) overexpressing or knockdown constructs and assessed osteogenic induction in the presence or absence of ICA. Sclerostin significantly inhibited BMSC proliferation and osteogenic differentiation, whereas the presence of ICA not only increased the number of viable BMSCs but also enhanced ALP activity and formation of calcium nodules during osteogenic induction. In addition, the osteogenic genes including Runx2, β-catenin, and c-myc as well as antioxidant factors (Prdx1, Cata, and Nqo1) were downregulated by sclerostin and restored by ICA treatment. Mechanistically, ICA exerted these effects by activating the Wnt/β-catenin pathway. In conclusion, ICA can promote the proliferation and osteogenic differentiation of BMSCs in situ and therefore may enhance the therapeutic efficiency of BMSC transplantation in OP. |
Databáze: | OpenAIRE |
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