P144 Effect of low-dose ionizing radiation on the inflammatory phenotype of adipocytes and differentiation of osteoclasts (in vitro). (March 2019)

• Record Type: Journal Article
• Authors: Shreder, K; Rapp, F; Kraft, D; Hassan, S; Fournier, C
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 1
• Page Start: A63
• Page End: A63
• Publication Date: 2019-03
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2019.127
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Career situation of first and presenting author: Post-doctoral fellow. Introduction: Adipose tissue is a complex endocrine organ that produces a variety of immune and inflammatory mediators. Adipocytes, the dominant cell type of adipose tissue, are known to support inflammatory processes in muskuloskeletal diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA) by release of different cytokines and adipokines. During this process, osteoclastogenesis is also enhanced and results in an imbalance of bone metabolism. Low-dose radiation therapy (LD-RT) is known to attenuate inflammation and to increase the mobility of patients suffering from RA or OA. 1 Objectives: In our previous work, we observed a decrease of visfatin levels in serum of patients treated with low-dose ionizing radiation during exposure to the alpha-emitter radon. 2 In the same study, a decrease of markers for bone resorption after radon exposure was detected. Based on this, we next compared the response of human adipocytes derived from subcutaneous and infrapatellar adipose tissue to ionizing radiation with respect to release of adipokines and other inflammatory factors (IL-6, IL-8). In parallel, we analyzed the effect of ionizing radiation on differentiation capacity of osteoclast (OC) precursors into mature, bone resorbing OC. Methods: Human subcutaneous predipocytes and human infrapatellar preadipocytes were irradiated with different doses of ionizing radiation, and release of inflammatory factors was measured in the cell culture supernatants using ELISA. OC precursors were isolated from human donor blood, differentiated according to standard protocols and analyzed by fluorescent stainings for cell nuclei, tartrate-resistant acidic phosphatase (TRAP) and actin filaments. Results: The results revealed that the release of adipokines and inflammatory cytokines (IL-6, IL-8) was not significantly affected by ionizing radiation. Further, it was found that differentiation of OC precursor cells into mature OC is reduced after irradiation. Conclusions: The observations made in this study suggest that adipocytes are probably not the main source of modified adipokine levels in the arthritic joint. However, an observed tendency of adipocytes to increase fat accumulation after irradiation suggests radiation-induced changes in functionality of human adipocytes which could have an indirect impact on the radiation response of the tissue. OC respond to radiation by reduced differentiation and structural changes, but the impact on functionality needs to be further tested. References: Frey B, et al. Cancer Lett 2015;368:230–237. Cucu A, Shreder K, et al. Front Immunol 2017;8:1–9. Acknowledgements: German Federal Ministry of Education and Research (02NUK017A). Disclosure of Interest: None declared.