06.03 Ionising radiation inhibits adipokine induced inflammation in synovial fibroblasts and differentiation of osteoclasts

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Abstract

Background

Musculoskeletal disorders (MSD) represent the highest cause of disability in Europe. Reduced mobility and quality of life are the consequences of cartilage and bone tissue destruction and chronic inflammation processes, driven by release of inflammatory factors including adipokines and bone destruction by osteoclasts. For the treatment of MSD primarily drugs are used. However, additional pain relieve is achieved when the patients receive low-dose radiation therapy with photons or radon spa treatment. To assess the effect of low-dose ionising radiation, we examined in vitro whether irradiation modifies the differentiation and activity of osteoclasts and affects the expression of inflammatory and bone destructive factors in adipokine stimulated synovial fibroblasts (SF).

Material and methods

Human SF from rheumatoid arthritis patients (RASF) and healthy donors (NSF) were pretreated with adipokines for 24 hour prior to irradiation with X-rays. Cell supernatants were collected 24 hour post-irradiation and inflammatory factors, known to contribute to the inflammation process (IL-6, IL-8, MMP-1), were measured. Human osteoclast precursor cells were X-irradiated and cultivated with M-CSF and RANKL either on bone slices or plastic for 21 days. Differentiated osteoclasts were defined as TRAP and F-actin positive with 3 or more nuclei (DAPI). TRAP activity was measured in cell supernatants.

Results

In vitro cultured primary NSF and RASF show an increased release of proinflammatory factors (IL-6, IL-8, MMP-1) after stimulation with adipokines. Irradiation of stimulated cells reduces the release of inflammatory factors in RASF, but not in NSF. Irradiation of osteoclast precursor cells caused an inhibition of osteoclast differentiation and changed activity of mature osteoclasts.

Conclusion

Synovial fibroblasts and osteoclasts play important roles in the synovial inflammation and bone degradation in arthritic joint. Our in vitro results suggest that the release of inflammatory factors in adipokine stimulated RASF and the number of osteoclasts can be reduced by low-dose X-ray irradiation, and therefore potentially inhibiting inflammation and bone destruction in the joint of patients with MSD.

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