Low‐dose γ‐radiation inhibits IL‐1β‐induced dedifferentiation and inflammation of articular chondrocytes via blockage of catenin signaling

• Published in: IUBMB life 2014-02, Vol.66 (2), p.128-137
• Main Authors: Hong, Eun‐Hee, Song, Jie‐Young, Lee, Su‐Jae, Park, In‐Chul, Um, Hong‐Duck, Park, Jong Kuk, Lee, Kee‐Ho, Nam, Seon Young, Hwang, Sang‐Gu
• Format: Article
• Language: English
• Subjects: Cartilage, Articular - radiation effects; catenin; Catenins - genetics; Catenins - metabolism; Cell Dedifferentiation - drug effects; Cell Dedifferentiation - radiation effects; chondrocytes; Chondrocytes - metabolism; Chondrocytes - radiation effects; dedifferentiation; Gamma Rays; Humans; inflammation; Inflammation - metabolism; Inflammation - pathology; Interleukin-1beta - pharmacology; low dose radiation; Radiation Dosage; Research Communications; Signal Transduction - radiation effects
• ISSN: 1521-6543; 1521-6551
• DOI: 10.1002/iub.1248

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)‐1β‐induced chondrocyte destruction without causing side effects, such as cell death and senescence. IL‐1β treatment induced an increase in the expression of α‐, β‐, and γ‐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‐κB pathway. Notably, LDR blocked cartilage disorders by inhibiting IL‐1β‐induced catenin signaling and subsequent catenin‐dependent suppression of the Sox‐9 pathway and activation of the NF‐κB 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. © 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