Low-dose gamma-radiation inhibits IL-1 beta-induced dedifferentiation and inflammation of articular chondrocytes via blockage of catenin signaling

Abstract

Although low-dose radiation (LDR) regulates a wide range of biological processes, limited information is available on the effects of LDR on the chondrocyte phenotype. Here, we found that LDR, at doses of 0.5-2 centiGray (cGy), inhibited interleukin (IL)-1 beta-induced chondrocyte destruction without causing side effects, such as cell death and senescence. IL-1 beta treatment induced an increase in the expression of alpha-, beta-, and gamma-catenin proteins in chondrocytes via Akt signaling, thereby promoting dedifferentiation through catenin-dependent suppression of Sox-9 transcription factor expression and induction of inflammation through activation of the NF-kappa B pathway. Notably, LDR blocked cartilage disorders by inhibiting IL-1 beta-induced catenin signaling and subsequent catenin-dependent suppression of the Sox-9 pathway and activation of the NF-kappa B pathway, without directly altering catenin expression. LDR also inhibited chondrocyte destruction through the catenin pathway induced by epidermal growth factor, phorbol 12-myristate 13-acetate, and retinoic acid. Collectively, these results identify the molecular mechanisms by which LDR suppresses pathophysiological processes and establish LDR as a potentially valuable therapeutic tool for patients with cytokine- or soluble factors-mediated cartilage disorders. (c) 2014 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 66(2):128-137, 2014