A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteoarthritis patients

Abstract

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 synovial 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.

Intergenerational thyroid hormone homeostasis imbalance in cerebellum of rats perinatally exposed to glyphosate‐based herbicide

“…Our results showed that carnitine metabolite presented significantly higher concentrations in 5 mg/kg treated animals ( p‐ value = .0086572) (Figure 8(A,B), Table 1), a dose that was also found to downregulate Thrβ1 . Thyroxin metabolite, which was also found to be significantly altered in animals exposed to the lower dose ( p ‐value = .0066903) (Figure 8(A,B), Table S1), have its regulation levels influenced by Dio3 , a gene that presented a significant expression alterations at 5 mg/kg treatment 59‐61 . Briefly, others metabolite concentrations significantly altered ( p ‐value < .05) in animals treated with different doses of GBH (Tables S1 and S2) could be a result of gene expression modifications influencing metabolite production, as observed by our gene‐metabolite correlation.…”

Dehydroepiandrostenedione sulphate (DHEAS) levels predict high risk of rheumatoid arthritis (RA) in subclinical hypothyroidism

“…There has been much interest in exploring therapeutic avenues to ameliorate non specific symptoms and improve this “localised” hypothyroidism [ 10 ]. Localized hypothyroidism of synovial cells have been documented in euthyroid subjects of RA to the extent that fT3 is nearly absent in synovial fluid [ 11 ]. Just like primary hypothyroidism, impaired QoL persist despite controlled disease activity in rheumatological diseases like RA, systemic lupus erythemtosus (SLE), Sjogren syndrome [ 12 ].…”

“…Although levothyroxine brings down the level of cytokines, they do not return to same level as healthy controls after euthyroid state is achieved [ 18 ]. Paradoxically, T4 (but not T3) may induce IL-6 production in synovial cells [ 11 ]. Since IL-6 is primary mediator in pathogenesis of rheumatoid arthritis [ 19 ]; this common pathogenetic link explains the usefulness of EULAR-CSA score in hypothyroidism.…”

Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice

“…The neuroendocrine and immune systems are closely interrelated, as the secretory products of the neuroendocrine system can act on the immune system and vice versa [1]. One example involves hormones that can regulate the immune system [2,3], such as prolactin (PRL) secreted by the pituitary gland, and extrapituitary immune system cells, such as T cells [4,5], B cells, antigen presenting cells (APCs) [6], natural killer cells [7,8], and monocytes/macrophages [9]. The immunostimulatory functions of PRL have been previously described.…”