title: The effects of anticholinergic insecticides on human mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are located primarily in the bone marrow and are characterized by their capacity to differentiate into mesenchymal lineages such as bone, fat, and cartilage in response to appropriate signals. Several signaling mechanisms act to control MSC survival, proliferation, and differentiation, and failure or disruption of these signaling pathways can lead to degenerative disease or neoplasia. Organophosphate (OP) and carbamate pesticides, which are used in large amounts in agriculture to control insects, are designed to disrupt acetylcholine signaling by inhibiting the enzyme acetylcholinesterase (AChE). Effects of OP and carbamate pesticides on the human central nervous system have been well documented. However, AChE is broadly distributed, and the effects of anticholinergic insecticides on nonnervous tissue have received little attention. In the present study we found that human MSCs express AChE, which makes these cells potential targets for AChE inhibiting agents. We therefore examined the effects of an OP pesticide, chlorpyrifos, and a carbamate, carbofuran, on MSC characteristics. It was found that micromolar concentrations of these anticholinergic insecticides had no effect on MSC survival or proliferation but limited MSC differentiation capacity by inhibiting osteogenic differentiation. These results demonstrate that exposure to micromolar concentrations of OP and carbamate pesticides may affect tissue turnover and pathophysiology by interfering with MSC regulation.
authors.affiliation: Biomedical Tissue Research Group, Department of Biology, University of York, Heslington, York, YO10 5YW, United Kingdom.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Paul G
authors.initials: PG
authors.lastname: Genever
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells; D002235:Carbofuran / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010011:Osteocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
chemical_list: D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000110:Acetylcholinesterase; D004390:Chlorpyrifos; D002235:Carbofuran