Biochemical and Biophysical Research Communications, Vol.508, No.1, 17-24, 2019
Effect of hypoxia/reoxygenation on the biological effect of IGF system and the inflammatory mediators in cultured synoviocytes
Hypoxia/reoxygenation (H/R) plays an important role in the pathogenesis of osteoarthritis. Fibroblast-like synoviocytes (FLS), which are highly sensitive to H/R, are thought to be associated with cartilage degradation during osteoarthritis development. In this study, we investigated the biological effects of insulin-like growth factor (IGF) system and the expression of inflammatory mediators in FLS. We also pretreated FLS with tumor necrosis factor-alpha (TNF-alpha) before H/R in order to observe the response of FLS with the background of inflammatory cytokines. H/R increased the levels of TNF-alpha-induced C-C chemokine ligand 5 (CCL5), interleukin-beta (IL-1 beta) and interleukin-6 (IL-6) in cell-free culture supernatants; H/R also increased the expression of TNF-alpha-induced insulin-like growth factor binding protein 3 (IGFBP-3), downregulated the expression of insulin-like growth factor 1 (IGF-1), promoted the loss of mitochondrial membrane potential (MMP), the openness of mitochondrial permeability transition pore (MPTP), the release of intracellular reactive oxygen species (ROS), and mitochondrial matrix swelling, outer membrane rupture and decrease in cristae. Furthermore, H/R induced the expression of catabolic factors and activated the NF-kappa B signaling pathway in FLS. We therefore concluded that H/R may play a role in inducing inflammation and increase the TNF-alpha-induced inflammatory effect in FLS, contributing to osteoarthritis pathogenesis. (C) 2018 Elsevier Inc. All rights reserved.