Abstract
BackgroundThis study investigated the role of Forkhead box Q1 (FOXQ1) in the osteogenic differentiation of bone mesenchymal stem cells.MethodsMouse bone mesenchymal stem cells (mBMSCs) were transfected with lentivirus to generate Foxq1-overexpressing mBMSCs, Foxq1-suppressed mBMSCs, and mBMSC controls. The activity of osteogenic differentiation was evaluated with alizarin red staining, alkaline phosphatase activity assay, and RT-qPCR. Wnt/β-catenin signaling activities were compared among groups by TOPFlash/FOPFlash assay, immunofluorescence staining, and western blot assay of beta-catenin (CTNNB1). Coimmunoprecipitation mass spectrometry was also carried out to identify proteins binding with FOXQ1.ResultsOur data showed that FOXQ1 expression was positively correlated with the osteogenic differentiation of the mBMSCs. FOXQ1 also promoted the nuclear translocation of CTNNB1 in the mBMSCs, enhancing Wnt/β-catenin signaling, which was also shown to be essential for the osteogenic differentiation-promoting effect of FOXQ1 in the mBMSCs. Annexin A2 (ANXA2) was bound with FOXQ1, and its depletion reversed the promoting effect of FOXQ1 on Wnt/β-catenin signaling.ConclusionThese results showed that FOXQ1 binds with ANXA2, promoting Wnt/β-catenin signaling in bone mesenchymal stem cells, which subsequently promotes osteogenic differentiation.
Highlights
This study investigated the role of Forkhead box Q1 (FOXQ1) in the osteogenic differentiation of bone mesenchymal stem cells
Our findings suggested that FOXQ1 promotes osteogenic differentiation of mouse bone mesenchymal stem cells via the Wnt/β-catenin signaling pathway
We showed that the influence of FOXQ1 on the osteogenic differentiation of mouse bone mesenchymal stem cells (mBMSCs) was partially reversed by counterregulating the activity of Wnt/β-catenin signaling, through the Wnt/β-catenin signaling suppressor DKK1 in the Foxq1-over mBMSC group or the Wnt/β-catenin signaling activator 6BIO in the Foxq1-sh mBMSC group
Summary
This study investigated the role of Forkhead box Q1 (FOXQ1) in the osteogenic differentiation of bone mesenchymal stem cells. Mesenchymal stem cells constitute a group of multipotent cells capable of differentiating into various types of cells, including osteoblasts, adipocytes, and various other types of cells. This process is modulated by various signaling pathways, including BMP [1], TGF-β [2], and the Wnt/β-. FOXQ1 regulates various physiological processes, including the survival [12] and proliferation of stem cells [13]; its role in osteogenic differentiation remains to be elucidated. Our findings suggested that FOXQ1 promotes osteogenic differentiation of mouse bone mesenchymal stem cells via the Wnt/β-catenin signaling pathway
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