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Icariin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying molecular mechanism by which Icariin regulates osteogenic differentiation needs to be further revealed. The viability of BMSCs was assessed by cell counting kit 8 assay. BMSC osteogenic differentiation ability was evaluated by detecting alkaline phosphatase activity and performing alizarin red S staining. The protein levels of osteogenic differentiation-related markers, sirtuin 1 (SIRT1), ubiquitin-specific protease 47 (USP47), and Wnt/β-catenin-related markers were determined using western blot. SIRT1 mRNA level was measured using quantitative real-time PCR. The regulation of USP47 on SIRT1 was confirmed by ubiquitination detection and co-immunoprecipitation analysis. Icariin could promote BMSC osteogenic differentiation. SIRT1 expression was enhanced by Icariin, and its knockdown suppressed Icariin-induced BMSC osteogenic differentiation. Moreover, deubiquitinating enzyme USP47 could stabilize SIRT1 protein expression. Besides, SIRT1 overexpression reversed the inhibiting effect of USP47 knockdown on BMSC osteogenic differentiation, and USP47 knockdown also restrained Icariin-induced BMSC osteogenic differentiation. Additionally, Icariin enhanced the activity of the Wnt/β-catenin pathway by upregulating SIRT1. Icariin facilitated BMSC osteogenic differentiation via the USP47/SIRT1/Wnt/β-catenin pathway.

Titel:	Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/β-catenin.
Autor/in / Beteiligte Person:	Wang, H ; Zhang, H ; Zhang, Y ; Wang, P
Link:	Zum Volltext
Zeitschrift:	Chemical biology & drug design, Jg. 103 (2024-02-01), Heft 2, S. e14431
Veröffentlichung:	Oxford : Wiley-Blackwell, 2006-, 2024
Medientyp:	academicJournal
ISSN:	1747-0285 (electronic)
DOI:	10.1111/cbdd.14431
Schlagwort:	Humans beta Catenin metabolism Cell Differentiation drug effects Cells, Cultured Ubiquitin Thiolesterase metabolism Ubiquitin-Specific Proteases metabolism Gene Knockdown Techniques Flavonoids pharmacology Mesenchymal Stem Cells cytology Mesenchymal Stem Cells drug effects Mesenchymal Stem Cells metabolism Osteogenesis drug effects Osteogenesis genetics Sirtuin 1 genetics Sirtuin 1 metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Chem Biol Drug Des] 2024 Feb; Vol. 103 (2), pp. e14431. MeSH Terms: Flavonoids* / pharmacology ; Mesenchymal Stem Cells* / cytology ; Mesenchymal Stem Cells* / drug effects ; Mesenchymal Stem Cells* / metabolism ; Osteogenesis* / drug effects ; Osteogenesis* / genetics ; Sirtuin 1* / genetics ; Sirtuin 1* / metabolism ; Humans ; beta Catenin / metabolism ; Cell Differentiation / drug effects ; Cells, Cultured ; Ubiquitin Thiolesterase / metabolism ; Ubiquitin-Specific Proteases / metabolism ; Gene Knockdown Techniques References: Bi, Z., Zhang, W., & Yan, X. (2022). Anti-inflammatory and immunoregulatory effects of icariin and icaritin. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 151, 113180. https://doi.org/10.1016/j.biopha.2022.113180. ; Chen, Y., Zhou, F., Liu, H., Li, J., Che, H., Shen, J., & Luo, E. (2021). 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Contributed Indexing: Keywords: BMSCs; Icariin; SIRT1; USP47; osteogenic differentiation Substance Nomenclature: 0 (beta Catenin) ; 0 (Flavonoids) ; VNM47R2QSQ (icariin) ; EC 3.5.1.- (SIRT1 protein, human) ; EC 3.5.1.- (Sirtuin 1) ; 0 (USP47 protein, human) ; EC 3.4.19.12 (Ubiquitin Thiolesterase) ; EC 3.4.19.12 (Ubiquitin-Specific Proteases) Entry Date(s): Date Created: 20240219 Date Completed: 20240223 Latest Revision: 20240325 Update Code: 20240325

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Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/β-catenin.