Benzo[a]pyrene Impedes Self-renewal and Differentiation of Mesenchymal Stem Cells and Influences Fracture Healing
Benzo[a]pyrene Impedes Self-renewal and Differentiation of Mesenchymal Stem Cells and Influences Fracture Healing
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苯并[a]芘阻碍间充质干细胞的自我更新和分化并影响骨折愈合
DOI：
10.1016/j.scitotenv.2017.02.152
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Yaguang Weng
中科院分区：
文献类型：
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作者：
Yiqing Zhou;Rong Jiang;Liqin An;Hong Wang;Sicheng Chen;Qiong Shi;Yaguang Weng
间充质干细胞（MSC）在骨折修复过程中参与骨形成过程。苯并[a]芘（BaP）-香烟烟雾成分和芳香烃受体的强大动力。（Ahr）-不利地影响骨状况和成骨细胞分化。首先我们注意到吸烟者骨髓间充质干细胞（human bone marrow mesenchymal stem，hBM-MSCs）的自我更新和分化能力下降，并通过上调Ahr靶基因细胞色素P450（CYP 1B 1）的表达激活MSCs中的Ahr信号。在体外研究中，我们使用C3 H10 T1/2和骨髓间充质干细胞（BM-MSCs）与BaP，发现BaP损害MSCs的固有特性。对MSC的进一步研究表明，BaP激活Ahr信号通路，抑制TGF-β1/SMAD 4和TGF-β1/ERK/AKT信号通路。相应的结果，胫骨骨折骨痂产生的苯并（a）芘给药的大鼠出现延迟愈合。白藜芦醇（一种天然的Ahr拮抗剂）在体内外均能阻断BaP的这种作用。这些数据表明，Ahr可能通过抑制SMAD依赖的信号通路TGF-β1/SMAD 4和SMAD非依赖的TGF-β1/ERK/AKT信号通路在BaP损伤的先天特性中发挥关键作用。白藜芦醇对BaP引起的骨髓间充质干细胞毒性有明显的抑制作用
Mesenchymal stem cells (MSCs) are implicated in the bone-forming process during fracture repair..Benzo[a]pyrene (BaP)—a cigarette smoke component and powerful motivator of the aryl hydrocarbon receptor.(Ahr)—unfavorably influences bone condition and osteoblast differentiation. The first thing we noticed decreases.self-renewal and differentiation of human bone marrow mesenchymal stem (hBM-MSCs) from smokers and activates Ahr signaling in MSCs by up-regulating the Ahr target gene cytochrome P450 (CYP) 1B1 expression. In.vitro studies, we employed C3H10T1/2 and bone marrow mesenchymal stem cells (BM-MSCs) with BaP and discovered that BaP impaired innate properties of MSCs. Further investigation into MSCs showed that exposure to.BaP activated Ahr signaling and inhibited TGF-β1/SMAD4 and TGF-β1/ERK/AKT signaling pathways. Corresponding with the outcomes, tibial fracture calluses produced by BaP-administered rats appeared to delay healing. This.effect of BaP was abrogated by resveratrol, a natural Ahr antagonist, in vitro and in vivo. These data demonstrated.that Ahr may play a key role in BaP–impaired innate properties by inhibiting SMAD-dependent signaling pathways TGF-β1/SMAD4 and SMAD-independent TGF-β1/ERK/AKT signaling pathways. Furthermore, resveratrol.inhibited MSCs from adverse effects caused by BaP