Icariin stimulates osteogenesis and suppresses adipogenesis of human bone mesenchymal stem cells via miR-23a-mediated activation of the Wnt/β-catenin signaling pathway.

Xu, Y ; Jiang, Y ; et al.

In: Phytomedicine : international journal of phytotherapy and phytopharmacology, Jg. 85 (2021-05-01), S. 153485

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Background: Icariin (ICA) is a bioactive compound isolated from epimedium-derived flavonoids that modulates bone mesenchymal stem cell osteogenesis and adipogenesis. However, its precise mechanism in this process is unknown.

Purpose: The purpose of this study was to elucidate the role of ICA on human bone mesenchymal stem cell (hBMSC) osteogenesis and adipogenesis by focusing on miR-23a mediated activation of the Wnt/β-catenin signaling pathway.

Methods: After ICA treatment, hBMSC osteogenesis and adipogenesis were evaluated using alkaline phosphatase staining, an alkaline phosphatase activity assay, Oil Red O staining, and cellular triglyceride levels. Moreover, the mRNA and protein expression levels of osteogenic and adipogenic markers as well as key factors of the Wnt/β-catenin signaling pathway were measured using quantitative reverse transcription polymerase chain reaction and western blotting. Lithium chloride, an activator of the Wnt/β-catenin signaling pathway, was used as a positive control. Finally, to investigate the role of miR-23a in ICA-induced activation of the Wnt/β-catenin signaling pathway, hBMSCs were transfected with miR-23a mimics or a miR-23a inhibitor.

Results: ICA significantly promoted hBMSC osteogenic differentiation by upregulating alkaline phosphatase activity and the expression of bone sialoprotein II (BSPII) and runt-related transcription factor-2 (Runx-2). In contrast, ICA inhibited hBMSC adipogenic differentiation by reducing lipid droplet formation and cellular triglyceride levels as well as by downregulating the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT enhancer-binding protein-α (C/EBP-α). ICA mediated its effects on hBMSCs by activating the Wnt/β-catenin signaling pathway. It did so by upregulating β-catenin, low density lipoprotein receptor-related protein 5 (LRP5), and T cell factor 1 (TCF1). Notably, the up-regulation of these proteins was blocked by Dickkopf-related protein 1 (DKK1). Critically, the effects of ICA on hBMSCs were similar to that of the positive control, lithium chloride. Notably, ICA-induced activation of the Wnt/β-catenin signaling pathway was significantly attenuated following miR-23a up-regulation. Conversely, miR-23a downregulation affected hBMSCs in the same manner as ICA; i.e., it activated the Wnt/β-catenin signaling pathway.

Conclusion: ICA promotes and inhibits, respectively, hBMSC osteogenesis and adipogenesis via miR-23a-mediated activation of the Wnt/β-catenin signaling pathway.

Titel:	Icariin stimulates osteogenesis and suppresses adipogenesis of human bone mesenchymal stem cells via miR-23a-mediated activation of the Wnt/β-catenin signaling pathway.
Autor/in / Beteiligte Person:	Xu, Y ; Jiang, Y ; Jia, B ; Wang, Y ; Li, T
Link:	Zum Volltext
Zeitschrift:	Phytomedicine : international journal of phytotherapy and phytopharmacology, Jg. 85 (2021-05-01), S. 153485
Veröffentlichung:	Stuttgart : Urban & Fischer Verlag ; <i>Original Publication</i>: Stuttgart ; New York : G. Fischer, c1994-, 2021
Medientyp:	academicJournal
ISSN:	1618-095X (electronic)
DOI:	10.1016/j.phymed.2021.153485
Schlagwort:	Bone and Bones cytology Cell Differentiation drug effects Cells, Cultured Core Binding Factor Alpha 1 Subunit metabolism Epimedium chemistry Humans Integrin-Binding Sialoprotein metabolism Mesenchymal Stem Cells cytology beta Catenin metabolism Adipogenesis drug effects Flavonoids pharmacology Mesenchymal Stem Cells drug effects MicroRNAs genetics Osteogenesis drug effects Wnt Signaling Pathway
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Phytomedicine] 2021 May; Vol. 85, pp. 153485. <i>Date of Electronic Publication: </i>2021 Jan 29. MeSH Terms: Wnt Signaling Pathway* ; Adipogenesis / drug effects ; Flavonoids / pharmacology ; Mesenchymal Stem Cells / drug effects ; MicroRNAs / genetics ; Osteogenesis / *drug effects ; Bone and Bones / cytology ; Cell Differentiation / drug effects ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit / metabolism ; Epimedium / chemistry ; Humans ; Integrin-Binding Sialoprotein / metabolism ; Mesenchymal Stem Cells / cytology ; beta Catenin / metabolism Contributed Indexing: Keywords: Adipogenesis; Human bone mesenchymal stem cells; Icariin; MicroRNA-23a; Osteogenesis; Wnt/β-catenin signaling pathway Substance Nomenclature: 0 (CTNNB1 protein, human) ; 0 (Core Binding Factor Alpha 1 Subunit) ; 0 (Flavonoids) ; 0 (Integrin-Binding Sialoprotein) ; 0 (MIRN23a microRNA, human) ; 0 (MicroRNAs) ; 0 (RUNX2 protein, human) ; 0 (beta Catenin) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210320 Date Completed: 20210518 Latest Revision: 20210518 Update Code: 20240513

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