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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.

Competing Interests: All the authors declare they have no competing interests.

Titel:	Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/ β -Catenin Signaling Pathway.
Autor/in / Beteiligte Person:	Gao, J ; Xiang, S ; Wei, X ; Yadav, RI ; Han, M ; Zheng, W ; Zhao, L ; Shi, Y ; Cao, Y
Link:	Zum Volltext
Zeitschrift:	BioMed research international, Jg. 2021 (2021-01-22), S. 6666836
Veröffentlichung:	New York, NY : Hindawi Pub. Co., 2021
Medientyp:	academicJournal
ISSN:	2314-6141 (electronic)
DOI:	10.1155/2021/6666836
Schlagwort:	Animals Antioxidants metabolism Bone Marrow Cells cytology Bone Morphogenetic Proteins genetics Cell Differentiation drug effects Cell Proliferation drug effects Cells, Cultured Drugs, Chinese Herbal pharmacology Female Gene Expression Regulation drug effects Genetic Markers genetics Mesenchymal Stem Cells metabolism Osteogenesis genetics Osteogenesis physiology Rats, Sprague-Dawley beta Catenin metabolism Rats Bone Morphogenetic Proteins metabolism Flavonoids pharmacology Mesenchymal Stem Cells drug effects Osteogenesis drug effects Wnt Signaling Pathway drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Biomed Res Int] 2021 Jan 22; Vol. 2021, pp. 6666836. <i>Date of Electronic Publication: </i>2021 Jan 22 (<i>Print Publication: </i>2021). MeSH Terms: Bone Morphogenetic Proteins / metabolism ; Flavonoids / pharmacology ; Mesenchymal Stem Cells / drug effects ; Osteogenesis / drug effects ; Wnt Signaling Pathway / *drug effects ; Animals ; Antioxidants / metabolism ; Bone Marrow Cells / cytology ; Bone Morphogenetic Proteins / genetics ; Cell Differentiation / drug effects ; Cell Proliferation / drug effects ; Cells, Cultured ; Drugs, Chinese Herbal / pharmacology ; Female ; Gene Expression Regulation / drug effects ; Genetic Markers / genetics ; Mesenchymal Stem Cells / metabolism ; Osteogenesis / genetics ; Osteogenesis / physiology ; Rats, Sprague-Dawley ; beta Catenin / metabolism ; Rats References: Free Radic Biol Med. 2018 Apr;118:1-12. (PMID: 29452246) ; Biomed Res Int. 2014;2014:569563. (PMID: 24524081) ; Dis Markers. 2016;2016:7067984. (PMID: 27594735) ; Endocr Connect. 2019 Jul;8(7):923-934. (PMID: 31234141) ; Int J Genomics. 2019 Jan 8;2019:7076513. (PMID: 30729116) ; Biomed Pharmacother. 2019 Apr;112:108746. (PMID: 30970530) ; Rheum Dis Clin North Am. 2018 Aug;44(3):437-451. (PMID: 30001785) ; Stem Cell Res Ther. 2019 Jan 22;10(1):37. (PMID: 30670092) ; J Bone Miner Res. 2013 Nov;28(11):2392-9. (PMID: 23661628) ; Int J Mol Sci. 2020 Jan 05;21(1):. (PMID: 31948061) ; J Nutr Biochem. 2017 Nov;49:42-52. (PMID: 28866105) ; Int J Mol Med. 2020 Mar;45(3):816-824. (PMID: 31985018) ; Oxid Med Cell Longev. 2019 Dec 12;2019:6493081. (PMID: 31915512) ; J Clin Endocrinol Metab. 2019 Jun 1;104(6):2443-2452. (PMID: 30759221) ; Ann Intern Med. 2017 Aug 1;167(3):ITC17-ITC32. (PMID: 28761958) ; Biomaterials. 2013 Dec;34(38):9998-10006. (PMID: 24079891) ; Int J Med Sci. 2013 Apr 23;10(6):782-9. (PMID: 23630444) ; Sci Rep. 2018 Nov 7;8(1):16456. (PMID: 30405156) ; J Bone Miner Metab. 2020 Sep 2;:. (PMID: 32880010) ; Am J Transl Res. 2019 Oct 15;11(10):6544-6552. (PMID: 31737205) ; Odontology. 2018 Oct;106(4):469-480. (PMID: 29713913) ; Yonsei Med J. 2019 Aug;60(8):751-759. (PMID: 31347330) ; Nanoscale. 2019 Nov 21;11(43):20884-20892. (PMID: 31660556) ; Molecules. 2014 Nov 14;19(11):18690-704. (PMID: 25405287) ; Elife. 2019 Sep 06;8:. (PMID: 31490121) ; J Steroid Biochem Mol Biol. 2015 Apr;148:225-31. (PMID: 25446885) ; Evid Based Complement Alternat Med. 2018 Sep 19;2018:3717391. (PMID: 30327678) ; Calcif Tissue Int. 2010 Sep;87(3):226-35. (PMID: 20614110) ; Int J Mol Sci. 2019 Nov 06;20(22):. (PMID: 31698687) ; Nat Rev Endocrinol. 2020 Jun;16(6):333-339. (PMID: 32203407) ; Osteoporos Int. 2019 Nov;30(11):2217-2223. (PMID: 31418061) ; J Bone Miner Res. 2009 Apr;24(4):578-88. (PMID: 19049336) ; J Cell Mol Med. 2018 Dec;22(12):6112-6121. (PMID: 30324718) ; Bone. 2017 Mar;96:29-37. (PMID: 27742498) ; Biosci Trends. 2018 Jul 17;12(3):275-281. (PMID: 29794404) Substance Nomenclature: 0 (Antioxidants) ; 0 (Bone Morphogenetic Proteins) ; 0 (Ctnnb1 protein, rat) ; 0 (Drugs, Chinese Herbal) ; 0 (Flavonoids) ; 0 (Genetic Markers) ; 0 (Sost protein, rat) ; 0 (beta Catenin) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210208 Date Completed: 20210524 Latest Revision: 20240226 Update Code: 20240226 PubMed Central ID: PMC7847333

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Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/ β -Catenin Signaling Pathway.