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4218359 
Journal Article 
Benzo[a]pyrene impedes self-renewal and differentiation of mesenchymal stem cells and influences fracture healing 
Zhou, Y; Jiang, R; An, L; Wang, H; Cheng, S; Qiong, S; Weng, Y 
2017 
1 
Science of the Total Environment
ISSN: 0048-9697
EISSN: 1879-1026 
ELSEVIER 
AMSTERDAM 
587-588 
305-315 
English 
28249752 
BCI:BCI201700491455 
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. 
Aryl hydrocarbon receptor; Benzo[a]pyrene; Fracture healing; Mesenchymal stem cells; Resveratrol