Low-dose γ-radiation inhibits IL-1β-induced dedifferentiation and inflammation of articular chondrocytes via blockage of catenin signaling.
Bottom Line: 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.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.
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.Show MeSH
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Mentions: To further determine whether the inhibitory effects of LDR on chondrocyte disorders are limited to the response to IL-1β, we incubated cells with three additional agents EGF, PMA, and RA previously reported to induce dedifferentiation of chondrocytes 16. Similar to the dedifferentiation and inflammation of chondrocytes caused by IL-1β treatment, the pathophysiological events induced by treatment with EGF, PMA, or RA, exemplified by the suppression of type II collagen and Sox-9 protein expression and induction of COX-2 protein expression, were associated with increased expression of β- and γ-catenin (Fig. 6, top). Notably, LDR at doses of both 0.5 and 1 cGy dramatically attenuated EGF-, PMA-, and RA-induced expression of all catenin proteins and subsequently normalized the altered expression of type II collagen, Sox-9, and COX-2 proteins produced by treatment with these agents (Fig. 6, middle). Consistent with these phenomena, LDR markedly attenuated the EGF-, PMA-, and RA-induced increase in Akt phosphorylation and thus reactivated GSK3β in chondrocytes (Fig. 6, bottom). These results demonstrate that LDR exerts an important inhibitory effect against the loss of the chondrocyte phenotype induced by different soluble factors.
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.