A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteoarthritis patients
A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteoarthritis patients
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DOI：
10.1038/s41598-019-49743-4
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发表时间：
2019-09-13
影响因子：
4.6
通讯作者：
Straub, Rainer H.
中科院分区：
文献类型：
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作者：
Poerings, Anna-Sophia;Lowin, Torsten;Straub, Rainer H.
虽然类风湿性关节炎（RA）患者有时会表现出甲状腺疾病，但甲状腺激素在炎症滑膜组织中的作用尚不清楚。这是相关的，因为甲状腺激素刺激免疫力，局部细胞可以通过脱碘酶（DIO）调节甲状腺激素水平。这项研究遵循的假设是，甲状腺激素网络的元素存在于滑膜组织中。在12例RA患者和32例骨关节炎（OA）患者中，我们使用血清、滑液、滑膜组织和滑膜成纤维细胞（SF），采用ELISA、免疫组织化学、成像方法、组织灌注研究、基于细胞的ELISA、流式细胞术和全基因组表达谱来表征局部甲状腺激素网络。RA和OA的血清/滑液甲状腺激素水平相似（入选标准：无甲状腺疾病）。血清中称为反向三碘甲状腺原氨酸（反向T3）的降解产物远低于滑液，表明甲状腺激素在滑液I环境中的生物降解。滑膜组织的灌流实验也证明了生物降解，特别是在RA中。甲状腺激素、DIO和甲状腺激素受体的细胞膜转运蛋白存在于组织和SF中。降解DIO阳性细胞密度在RA中高于OA。TNF增加RASF和OASF中降解DIO的蛋白表达。RASF的基因表达研究显示，生物活性T3的基因调控不显著。RA和OA滑膜组织/SF显示局部甲状腺激素网络。甲状腺激素在滑膜中发生强烈的生物降解。虽然生物活性T3不影响SF基因表达，但SF似乎对甲状腺激素具有中继功能。
While patients with rheumatoid arthritis (RA) sometimes demonstrate thyroidal illness, the role of thyroid hormones in inflamed synovial tissue is unknown. This is relevant because thyroid hormones stimulate immunity, and local cells can regulate thyroid hormone levels by deiodinases (DIO). The study followed the hypothesis that elements of a thyroid hormone network exist in synovial tissue. In 12 patients with RA and 32 with osteoarthritis (OA), we used serum, synovial fluid, synovial tissue, and synovial fibroblasts (SF) in order to characterize the local thyroid hormone network using ELISAs, immunohistochemistry, imaging methods, tissue superfusion studies, cell-based ELISAs, flow cytometry, and whole genome expression profiling. Serum/synovial fluid thyroid hormone levels were similar in RA and OA (inclusion criteria: no thyroidal illness). The degradation product termed reverse triiodothyronine (reverse T3) was much lower in serum compared to synovial fluid indicating biodegradation of thyroid hormones in the synovia I environment. Superfusion experiments with synovial tissue also demonstrated biodegradation, particularly in RA. Cellular membrane transporters of thyroid hormones, DIOs, and thyroid hormone receptors were present in tissue and SF. Density of cells positive for degrading DIOs were higher in RA than OA. TNF increased protein expression of degrading DIOs in RASF and OASF. Gene expression studies of RASF revealed insignificant gene regulation by bioactive T3. RA and OA synovial tissue/SF show a local thyroid hormone network. Thyroid hormones undergo strong biodegradation in synovium. While bioactive T3 does not influence SF gene expression, SF seem to have a relay function for thyroid hormones.