Different Secretory Activity of Articular and Subcutaneous Adipose Tissues from Rheumatoid Arthritis and Osteoarthritis Patients (original) (raw)

Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network

Annals of the Rheumatic Diseases, 2012

Objectives (1) To compare spontaneous and stimuliinduced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological activity of AAT and SM released factors. Methods Tissues were obtained from patients undergoing joint replacement surgery. Tissue explants were treated with proinfl ammatory cytokines relevant to RA pathogenesis (interleukin 1β (IL-1β), tumour necrosis factor (TNF), interferon γ, IL-15, IL-17, IL-23). Selected adipocytokine (TNF, IL-6, IL-8, IL-1β, IL-1Ra, adiponectin, leptin) concentrations were measured in culture supernatants using ELISA. The biological activity of tissue-conditioned media was evaluated by measuring production of selected factors (IL-6, IL-8, Dickkopf-1, osteoprotegerin) by fi broblast-like synoviocytes (FLS). Results Spontaneous cytokine release from AAT was ≤12% of that produced by SM, while leptin was secreted in similar amounts. AAT was highly reactive to proinfl ammatory cytokines (IL-1β>TNF). AAT treated with IL-1β released four times more leptin, similar amounts of IL-6 and IL-8 and about 20% of TNF, as compared with SM. Upon activation, the IL-1 receptor antagonist (IL-1Ra)/IL-1β ratio was higher in AAT than in SM cultures. Irrespective of activation status, SM produced twice as much adiponectin as AAT. Conditioned media from AAT and SM cultures similarly upregulated IL-6, IL-8, Dickkopf-1 and osteoprotegerin production by rheumatoid FLS. Conclusion Rheumatoid AAT is highly reactive tissue which upon stimulation secretes considerable amounts of proinfl ammatory (IL-6, IL-8, TNF) and anti-infl ammatory (IL-1Ra) cytokines and classical adipokines. This tissue releases biologically active factors that intensify pathogenic activities of rheumatoid FLS. Thus, AAT should be considered an important contributor to the pathological processes taking place in the RA joint.

Secretory activity of subcutaneous abdominal adipose tissue in male patients with rheumatoid arthritis and osteoarthritis - association with clinical and laboratory data

Reumatologia, 2016

Adipose tissue exerts widespread effects on the metabolism and immune system, but its activity differs between the genders. In the general population low-grade adipose tissue inflammation contributes to development of diseases of affluence. Little is known about the systemic impact of peripheral fat tissue in osteoarthritis (OA) and rheumatoid arthritis (RA), characterized by chronic, low- and high-grade systemic inflammation, respectively. To clarify this we evaluated the secretory activity of subcutaneous abdominal adipose tissue (SAAT) obtained from male patients affected with RA (n = 21) and OA (n = 13), and assessed its association with body mass and composition, demographic, clinical and laboratory data. Basal and interleukin (IL)-1β-triggered secretion of selected adipocytokines from SAAT explants was measured by specific enzyme-linked immunosorbent assays (ELISA). Patients' body composition was evaluated by bioelectric impendence technique. Rheumatoid SAAT secreted more ...

Articular adipose tissue resident macrophages in rheumatoid arthritis patients: potential contribution to local abnormalities

Rheumatology (Oxford, England), 2013

The objectives of this study were to characterize macrophages resident in inflamed articular adipose tissue (AAT) and non-inflamed subcutaneous adipose tissue (ScAT) of RA patients and to evaluate the basal and cytokine-triggered secretory activities of these tissues. Tissues were obtained from patients undergoing knee joint replacement surgery. The number of total CD68(+), CD14(+) and CD163(+) macrophages was evaluated by immunohistochemistry. The concentrations of select factors were measured in supernatants from untreated and cytokine-treated tissue explant cultures using ELISA. IL-1β and TNF were applied as the stimuli. Paired samples of AAT and ScAT, obtained from the same patients, contained a similar number of macrophages, displaying an M2-skewed phenotype. Both tissues released equivalent amounts of IL-1β, TNF, IL-10 and macrophage migration inhibitory factor (MIF). However, AAT secreted more chemokines (CCL2, CCL5), cytokines [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra)],...

Adipocytokines in Rheumatoid Arthritis: The Hidden Link between Inflammation and Cardiometabolic Comorbidities

Journal of Immunology Research

Rheumatoid arthritis is a chronic autoimmune disease affecting typically synovial joints and leading to progressive articular damage, disability, and reduced quality of life. Despite better recent therapeutic strategies improving long-term outcomes, RA is associated with a high rate of comorbidities, infections, malignancies, and cardiovascular disease (CVD). Remarkably, some well-known pathogenic proinflammatory mediators in RA, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), may play a pivotal role in the development of CVD. Interestingly, different preclinical and clinical studies have suggested that biologic agents commonly used to treat RA patients may be effective in improving CVD. In this context, the contribution of adipocytokines has been suggested. Adipocytokines are pleiotropic molecules, mainly released by white adipose tissue and immune cells. Adipocytokines modulate the function of different tissues and cells, and in addition to energy homeostasis and m...

Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part II: Inflammatory background of osteoarthritis

Journal of Ultrasonography, 2013

Streszczenie Choroba zwyrodnieniowa stawów jest najczęstszą chorobą reumatyczną. Może się rozwijać jako pierwotne schorzenie narządu ruchu lub wtórnie w przebiegu innych zapalnych chorób stawów. Podobnie jak w przypadku większości chorób reumatycznych patogeneza choroby zwyrodnieniowej stawów nie została w pełni wyjaśniona. O tym, że istotną rolę w jej rozwoju odgrywają adipocytokiny, czyli mediatory zapalne produkowane w tkance tłuszczowej, wiadomo od kilku lat, a procesy zapalne zachodzące w tkance tłuszczowej, prowadzące do rozwoju zmian zwyrodnieniowych, są wiodącym tematem badań wielu laboratoriów immunologicznych. Zmianom degeneracyjnym u chorych na chorobę zwyrodnieniową często towarzyszy wtórny proces zapalny z obecnością nacieków komórkowych w błonie maziowej. W wielu przypadkach duże nasilenie zmian zapalnych jest podobne jak w innych jednostkach chorobowych, zwłaszcza w reumatoidalnym zapaleniu stawów, co utrudnia różnicowanie przy użyciu badań obrazowych. Może to mieć znaczące implikacje kliniczne, np. w odniesieniu do ultrasonografi i, która jest podstawowym badaniem obrazowym w diagnostyce, monitorowaniu skuteczności leczenia czy w potwierdzaniu remisji u chorych na reumatoidalne zapalenie stawów. W niniejszym artykule omówiono patogenezę trzech elementów obrazu chorobowego choroby zwyrodnieniowej stawów, tj. zapalenia błony maziowej, z uwagi na trudności różnicowania synovitis w przebiegu tej choroby i reumatoidalnego zapalenia stawów, oraz osteofi tów i podchrzęstnej sklerotyzacji, ze względu na istotne znaczenie czynnika zapalnego w ich powstawaniu.

The role of adipose tissue secretion in the creation and pain level in osteoarthritis

Endocrine Regulations

Objectives. With increasing evidence regarding the metabolic basis of osteoarthritis (OA), we studied the relationship between adipose tissue and OA. Methods. This study is part of an OA registry in the eastern part of Fars Province, Iran. Overall, 150 patients with OA and 300 sex matched individuals were selected as a control group. They were compared regarding adipokine concentration (leptin, adiponectin, resistin and visfatin), anthropo-metric indices, the Western Ontario and McMaster universities arthritis index score (WOMAC). Results. All adipokine levels were higher among OA patients (p<0.001). After adjusting for age, sex, and body mass index (BMI), adipokines showed a significant and positive association with OA (B: 14.12, B: 9.92, B: 24.71 and B: 12.29 for leptin, adiponectin, visfatin, and resistin, respectively; p<0.001). Except the adiponectin that had a negative relationship with BMI in the OA group (r=–0.570, p<0.001), other adipokines had positive relationshi...

Beyond fat mass: Exploring the role of adipokines in rheumatic diseases

TheScientificWorldJournal, 2011

The cloning of leptin in 1994 by Zhang et al. introduced a novel concept about white adipose tissue (WAT) as a very dynamic organ that releases a plethora of immune and inflammatory mediators, such as adipokines and cytokines, which are involved in multiple diseases. Actually, adipokines exert potent modulatory actions on target tissues involved in rheumatic diseases including cartilage, synovial, bone and immune cells. The goal of this paper is to elucidate the recent findings concerning the involvement of adipokines in rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and systemic lupus erythematosus (SLE).

Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase-13 expression in fibroblast-like synoviocytes more than proinflammatory mediators

Arthritis Research & Therapy, 2009

Introduction The role of adiponectin in the pathogenesis of arthritis is still controversial. This study was performed to examine whether adiponectin is involved in joint inflammation and destruction in rheumatoid arthritis (RA) in relation to the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Methods Synovial cells from RA patients were treated with adiponectin or interleukin (IL)-1β for 24 hours. The culture supernatant was collected and analyzed for the levels of IL-6, IL-8, prostaglandin E 2 (PGE 2), VEGF, and MMPs by enzyme-linked immunosorbent assay. The levels of adiponectin, VEGF, MMP-1, and MMP-13 in the joint fluids from 30 RA or osteoarthritis (OA) patients were also measured. Results Adiponectin at the concentration of 10 μg/mL stimulated the production of IL-6, IL-8, and PGE 2 in RA fibroblast-like synoviocytes (FLSs), although the level of these was much lower than with 1 ng/mL IL-1β. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1β. In addition, the level of adiponectin and MMP-1 in the joint fluid of RA patients was significantly higher than in OA patients. Adiponectin was positively correlated with VEGF in RA patients but not in OA patients, while the level of MMPs in joint fluid was not correlated with adiponectin in either RA or OA patients. Conclusions Adiponectin may play a significant role in the pathogenesis of RA by stimulating the production of VEGF and MMPs in FLSs, leading to joint inflammation and destruction, respectively.