title: Protective effect of short-term treatment with parathyroid hormone 1-34 on oxidative stress is involved in insulin-like growth factor-I and nuclear factor erythroid 2-related factor 2 in rat bone marrow derived mesenchymal stem cells.
abstract: Bone marrow-derived mesenchymal stem cell (MSC)-mediated regeneration is a promising treatment for degenerative disease and traumatic injuries. MSCs can be isolated from rats using magnetic-activated cell sorting with CD105 antibody. We investigated the relationships between the expression of endogenous insulin-like growth factor-I (IGF-I) and nuclear factor erythroid 2-related factor 2 (Nrf-2) during short-term treatment with parathyroid hormone (PTH) 1-34-induced protective response in MSCs. PTH 1-34 (10(-9)M) decreased reactive oxygen species (ROS) generation but increased cell viability and endogenous IGF-I (p<0.01). Suppression of IGF-I and Nrf-2 using specific small interfering RNA (siRNA) blocked the effects of PTH 1-34. Furthermore, increasing cell viability of PTH against hydrogen peroxide (H2O2) was suppressed by treatment with siRNA to IGF-I and Nr-2 (p<0.05). Exogenous IGF-I (10(-9)M) also increased endogenous IGF-I, cell viability, and Nrf-2 expression. These incremental increases were lessened by Nrf-2 siRNA (p<0.05). Exogenous IGF-I also inhibited the increase of H2O2-induced ROS generation, and the decrease of PTH 1-34-induced ROS generation in the presence of IGF-I and Nrf-2 siRNA. The increase of PTH 1-34-induced Nrf-2 expression was more significant in the nucleus than in the cytosol (p<0.05). PTH 1-34 also inhibited H2O2-induced inducible nitric oxide synthase expression, but increased the expression of heme oxygenase 1/2. The results implicate PTH 1-34, Nrf-2, and IGF-I signaling pathways in the response to oxidative stress. These factors could influence IGF-I regulation of metabolic fate and survival in MSCs.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine/Bio-Safety Research Institute, Chonbuk National University, South Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Oh
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine/Bio-Safety Research Institute, Chonbuk National University, South Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine/Bio-Safety Research Institute, Chonbuk National University, South Korea. Electronic address: cwkang@chonbuk.ac.kr.
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Kang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D034741:RNA, Small Interfering; D011863:Radioimmunoassay; D051381:Rats
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010281:Parathyroid Hormone; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I
keywords: HO-1/2; Inducible nitric oxide synthase; Insulin-like growth factor-I; Mesenchymal stem cells; Nrf-2; Oxidative stress