Association of Fpr1 gene expression with osteogenesis and adipogenesis of adipose derived stem cells.
Association of Fpr1 gene expression with osteogenesis and adipogenesis of adipose derived stem cells.
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DOI：
10.1016/j.bbrc.2021.08.044
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发表时间：
2021-10-15
影响因子：
3.1
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Xiao W;Le Q;Zhu D;Dighe A;Cui Q;Yang X
甲酰肽受体(FPR)在多种细胞功能中发挥重要作用，包括促进成骨和骨折愈合。本研究探讨了FPR1基因在脂肪干细胞成骨和成脂分化中的作用。FPR1基因敲除小鼠(KO)和野生型(WT)小鼠的原代ADSCs(MADSCs)和人ADSCs(HADSCs)分别用成骨(OM)和成脂(AM)培养液处理，并以基础培养液为对照。通过组织学和生化方法检测成骨和成脂情况。在hADSCs和mADSCs中，成骨诱导后FPR1基因表达增加，成骨基因表达增加，矿化增加。与WT ADSCs相比，KO ADSCs的成骨能力显著降低，成骨标志物表达、碱性磷酸酶活性和矿化水平降低。与WT ADSCs相比，KOADSCs的成脂作用明显增强，形成更多的脂滴，成脂标志物PPARγ和APP2的表达增加。核转录因子Forkhead box Protein O1(FoxO1)在KO ADSCs中表达降低，OM和AM分别引起FoxO1表达增加和降低。目前的研究揭示了FPR1基因的表达与mADSCs的成骨和成脂相关，其机制与FoxO1有关。我们目前的研究表明，靶向FPR1可能是促进ADSCs成骨的一种新策略。
Formyl peptide receptors (Fprs) play fundamental roles in multiple cell functions including promotion of osteogenesis and bone fracture healing. In this study, the role of Fpr1 gene in osteogenic and adipogenic differentiation of adipose derived stem cells (ADSCs) was investigated. Primary ADSCs (mADSCs) from either Fpr1 knockout (KO) or wild type (WT) mice and human ADSCs (hADSCs) were treated by osteogenic (OM) or adipogenic (AM) medium, with basal medium as control. Osteogenesis and adipogenesis were measured by histological and biochemical methods. In both hADSCs and mADSCs, Fpr1 gene expression, osteogenic gene expression, as well as mineralization were increased after osteogenic induction. The osteogenic capacity of KO ADSCs was remarkably reduced compared to WT ADSCs, with decreased levels of expression of osteogenic markers, alkaline phosphatase activity, and mineralization. In contrast, the adipogenesis of KO ADSCs was remarkably enhanced compared with WT ADSCs, forming more lipid droplets, and increasing expression of adipogenic markers PPARγ and aP2. Expression of the nuclear transcription factor Forkhead box protein O1 (FoxO1) was decreased in KO ADSCs, while OM and AM caused increase and decrease in FoxO1 expression, respectively. The current study revealed a correlation of Fpr1 gene expression with osteogenesis and adipogenesis of mADSCs, underlying a mechanism involving FoxO1. Our present research suggests that targeting Fpr1 might be a novel strategy to enhance osteogenesis of ADSCs.
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