title: Benzo[a]pyrene impedes self-renewal and differentiation of mesenchymal stem cells and influences fracture healing.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Liqin
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Sicheng
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: anniesq8718@aliyun.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiong
authors.affiliation: Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: yaguangweng@126.com.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D017102:Fracture Healing / Q000187:drug effects*; D059630:Mesenchymal Stem Cells; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene
keywords: Aryl hydrocarbon receptor; Benzo[a]pyrene; Fracture healing; Mesenchymal stem cells; Resveratrol