title: Low-dose γ-radiation inhibits IL-1β-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)-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.
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea; Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Hong
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Park
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D002358:Cartilage, Articular / Q000528:radiation effects; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation / Q000187:drug effects / Q000528:radiation effects*; D019902:Chondrocytes / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000494:pharmacology; D011829:Radiation Dosage; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D051177:Catenins; D053583:Interleukin-1beta
keywords: catenin; chondrocytes; dedifferentiation; inflammation; low dose radiation