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.