Etiology and Pathogenesis of Rheumatoid Arthritis-Interstitial Lung Disease.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast-myofibroblast transition, epithelial-mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Effects of aging-induced obesity on the transcriptional expression of adipogenesis and thermogenic activity in the gonadal white adipose, brown adipose, and skeletal muscle tissues.

PURPOSE: Aging is closely associated with chronic metabolic diseases, such as obesity, which lead to increased adiposity, skeletal muscle wasting, and imbalanced cellular energy metabolism. However, transcriptional profiles representing energy imbalances in aging-induced obesity are not fully understood. Thus, this study aimed to investigate the candidate genes predominantly regulated in aging-related obesity in spontaneously aged mice. METHODS: Male C57BL/6J mice were divided into three age groups according to age: 2- (young), 12- (middle-aged), and 24- (old) months. Body weight and body composition parameters were measured in all mice. Gonadal white adipose tissue (gWAT), brown adipose tissue (BAT), and skeletal muscle (SM) were dissected and weighed. The target tissues were assessed using biochemical and histological assays. RESULTS: Aging-induced obesity increased adipose mass and decreased SM weight through processes of adipocyte hypertrophy; however, recruitment of modulating adipogenesis-inducing transcription factors did not occur. Among adipokines, leptin level was greatly increased in the gWAT during aging. Interestingly, the ß2-adrenergic receptor had a higher affinity than the ß3-adrenergic receptor in aging-induced obesity. For the thermogenic regulation through ß-adrenergic receptors (ß-ARs), a declined uncoupling protein-1 (UCP-1) in the BAT was relevant to aging-induced obesity. CONCLUSION: Aging-induced obesity increases leptin levels in adipocytes and decreases UCP-1 in BAT through ß-ARs, according to transcriptional gene profiling. WAT browning increases energy expenditure due to exercise training adaptations. Further research is needed to discover more effective methods, such as exercise, against aging-induced obesity.

Switching from TNFα inhibitor to tacrolimus as maintenance therapy in rheumatoid arthritis after achieving low disease activity with TNFα inhibitors and methotrexate: 24-week result from a non-randomized, prospective, active-controlled trial.

BACKGROUND: Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). METHODS: This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. RESULTS: In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. CONCLUSION: This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. TRIAL REGISTRATION: Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.

The bone bridge significantly affects the decrease in bone mineral density measured with quantitative computed tomography in ankylosing spondylitis.

INTRODUCTION AND OBJECTIVE: Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction. METHODS: Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed. RESULTS: A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05). CONCLUSION: Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.

Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics.

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become a worldwide pandemic. Symptoms range from mild fever to cough, fatigue, severe pneumonia, acute respiratory distress syndrome (ARDS), and organ failure, with a mortality rate of 2.2%. However, there are no licensed drugs or definitive treatment strategies for patients with severe COVID-19. Only antiviral or anti-inflammatory drugs are used as symptomatic treatments based on clinician experience. Basic medical researchers are also trying to develop COVID-19 therapeutics. However, there is limited systematic information about the pathogenesis of COVID-19 symptoms that cause tissue damage or death and the mechanisms by which the virus infects and replicates in cells. Here, we introduce recent knowledge of time course changes in viral titers, delayed virus clearance, and persistent systemic inflammation in patients with severe COVID-19. Based on the concept of drug reposition, we review which antiviral or anti-inflammatory drugs can effectively treat COVID-19 patients based on progressive symptoms and the mechanisms inhibiting virus infection and replication.

Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1α Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link.

Sarcopenic obesity (SOB), which is closely related to being elderly as a feature of aging, is recently gaining attention because it is associated with many other age-related diseases that present as altered intercellular communication, dysregulated nutrient sensing, and mitochondrial dysfunction. Along with insulin resistance and inflammation as the core pathogenesis of SOB, autophagy has recently gained attention as a significant mechanism of muscle aging in SOB. Known as important cellular metabolic regulators, the AMP-activated protein kinase (AMPK) and the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) signaling pathways play an important role in autophagy, inflammation, and insulin resistance, as well as mutual communication between skeletal muscle, adipose tissue, and the liver. Furthermore, AMPK and PGC-1α signaling pathways are implicated in the gut microbiome-muscle axis. In this review, we describe the pathological link between SOB and its associated complications such as metabolic, cardiovascular, and liver disease, falls and fractures, osteoarthritis, pulmonary disease, and mental health via dysregulated autophagy controlled by AMPK and/or PGC-1α signaling pathways. Here, we propose potential treatments for SOB by modulating autophagy activity and gut dysbiosis based on plausible pathological links.

Predicting Imaging Remission in Rheumatoid Arthritis: a Case-control Ultrasound Study.

BACKGROUND: To elucidate the achievement rates of imaging remission and to examine the characteristics associated with imaging remission status among patients with rheumatoid arthritis (RA) who have attained clinical remission. METHODS: Ninety-seven patients with RA patients who had attained clinical remission, defined by DAS28-ESR < 2.6 were enrolled. Power Doppler ultrasonography (PDUS) was performed on 16 joints and 2 tendons, including the first to third metacarpophalangeal, second and third proximal interphalangeal, radiocarpal (RC), second and third metatarsophalangeal joints, and extensor carpi ulnaris tendons. They were graded based on a dichotomous assessment. The clinical and laboratory data of patients who had attained imaging remission were compared to those of patients who had attained only clinical remission. RESULTS: The imaging remission rate was 51.5% in patients who had attained clinical remission. Forty-seven patients (48.5%) were PDUS positive. Power Doppler was detected most frequently in the right RC joint (n = 40). PDUS positive patients had higher evaluator global assessment (EGA) scores (P < 0.001) than PDUS negative patients. PDUS positive patients also had higher clinical disease activity index and simplified clinical disease activity index scores than PDUS negative patients. Patients who had attained imaging remission had lower pain scores and used nonsteroidal anti-inflammatory drugs less frequently. Patients who had attained imaging remission had higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide levels. A low EGA score was found to be a predictor of imaging remission achievement among patients who had attained clinical remission. CONCLUSION: Only 51.5% of the patients with RA who had attained clinical remission were also in imaging remission. Patients who had attained imaging remission had lower EGA scores and higher RF levels than patients who had attained only clinical remission.

Taurine Stimulates Thermoregulatory Genes in Brown Fat Tissue and Muscle without an Influence on Inguinal White Fat Tissue in a High-Fat Diet-Induced Obese Mouse Model.

This study was conducted to investigate if taurine supplementation stimulates the induction of thermogenic genes in fat tissues and muscles and decipher the mechanism by which taurine exerts its anti-obesity effect in a mildly obese ICR (CD-1®) mouse model. Three groups of ICR mice were fed a normal chow diet, a high-fat diet (HFD), or HFD supplemented with 2% taurine in drinking water for 28 weeks. The expression profiles of various genes were analyzed by real time PCR in interscapular brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), and the quadriceps muscles of the experimental groups. Genes that are known to regulate thermogenesis like PGC-1α, UCP-1, Cox7a1, Cox8b, CIDE-A, and ß1-, ß2-, and ß3-adrenergic receptors (ß-ARs) were found to be differentially expressed in the three tissues. These genes were expressed at a very low level in iWAT as compared to BAT and muscle. Whereas, HFD increased the expression of these genes. Taurine supplementation stimulated the expression of UCP-1, Cox7a1, and Cox8b in BAT and only Cox7a1 in muscle, while there was a decrease in iWAT. In contrast, fat deposition-related genes, monoamine oxidases (MAO)-A, and -B, and lipin-1, were decreased by taurine supplementation only in iWAT and not in BAT or muscle. In conclusion, the potential anti-obesity effects of taurine may be partly due to upregulated thermogenesis in BAT, energy metabolism of muscle, and downregulated fat deposition in iWAT.

Effects of Chronic Intake of a Low Concentration of Taurine on Physical Strength and Body Composition in Mice.

Most studies of taurine on athletic performance have been conducted at acute and high doses in rodents. These doses and duration of administration are not reasonable for normal human life. Thus, it is not valid to extrapolate these animal results to people. Dose and duration that mimic human use of taurine in normal life can help to clarify the taurine effect in humans. This study investigated whether long-term, low-dose taurine (2% taurine drinking water for 25 weeks), similar to normal taurine intake in humans, can affect endurance exercise and body composition. Twenty ICR mice were divided into two groups. The control group received normal drinking water, and the taurine treated group received 2% taurine drinking water for 25 weeks. The mice were evaluated for body composition by mass and for physical strength by treadmill exhaustion and suspension tests. The supply of chronic 2% taurine drinking water has a slight effect on weight gain. In body composition analysis, a slight increase in body weight was due to an increase in muscle mass, not an increase in body fat. However, taurine ingestion did not increase endurance exercise. In conclusion, these results indirectly suggest that acute, high-dose taurine treatment is better than long-term, low-dose treatment to increase athletic performance.

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

BACKGROUND: To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). METHODS: This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. RESULTS: A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). CONCLUSIONS: Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.

Endocan as a marker of microvascular inflammation in kidney transplant recipients.

Endocan is a water-soluble proteoglycan exclusively secreted by vascular endothelium. Endocan levels may be elevated in kidney transplant recipients experiencing antibody-mediated rejection (ABMR), which is characterized by vascular inflammation in transplanted kidney. We evaluated the clinical relevance of endocan as markers of microvascular inflammation in patients who underwent kidney transplantation. Plasma and urinary endocan levels were measured in 203 kidney transplant recipients and were compared across different etiologies of allograft dysfunction and various pathologic scores. Both plasma and urinary endocan levels were significantly higher in patients with acute ABMR than those in patients with normal pathology, acute tubular necrosis (ATN), acute pyelonephritis, BK virus associated nephropathy (BKVN), and T-cell mediated rejection (TCMR). Patients with chronic active ABMR also exhibited significantly higher plasma and urinary endocan levels than patients with long-term graft survival. Scores of glomerulitis and peritubular capillaritis, which are typical features of microvascular inflammation, were significantly elevated in patients with higher plasma and/or urinary endocan levels. Furthermore, plasma and urinary endocan levels could effectively discriminate ABMR from ATN, BKVN, and TCMR. Finally, patients exhibiting high urinary and plasma endocan levels in acute ABMR group showed significantly worse renal survival. Altogether, plasma and urinary endocan levels may serve as potential markers of microvascular inflammation in kidney transplant recipients.

Anti-obesity effect of taurine through inhibition of adipogenesis in white fat tissue but not in brown fat tissue in a high-fat diet-induced obese mouse model.

This study was conducted to evaluate the anti-obesity effects of long-term taurine supplementation in a mild obese ICR mouse model and to study the mechanism by which taurine induces weight loss. Three groups of male ICR mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with 2% taurine in drinking water for 28 weeks. Body weight was measured every week. Metabolic, behavioral, and physiological monitoring were carried out using PhenoMaster at 28 weeks. Interscapular brown fat (BAT), inguinal white fat tissue (WAT), and quadriceps muscle were analyzed and compared to assess the change of gene expression related to adipogenesis. Taurine supplementation showed the trend of anti-obesity effect in ICR mice fed an HFD for 28 weeks. HFD-fed mice did not show significant difference of oxygen consumption (VO2), energy expenditure (EE), respiratory exchange rate (RER), and locomotive activity compared with those of normal chow diet fed mice. The expression of adipogenesis-related genes such as PPAR-α, PPAR-γ, C/EBP-α, C/EBP-ß, and AP2 increased in BAT and WAT, but not in muscle tissue. Taurine supplementation showed the downregulation of these genes in WAT but not in BAT or muscle. Consistently, the expression of taurine transporter (TauT) and adipocyte-specific genes such as adiponectin, leptin, and IL-6 was regulated in a similar pattern by taurine supplementation. Long-term taurine supplementation causes weight loss, most likely by inhibiting adipogenesis in WAT. TauT expression may be involved in the expression of various genes regulated by taurine supplementation.

Potential therapeutic antibodies targeting specific adiponectin isoforms in rheumatoid arthritis.

BACKGROUND: Different adiponectin isoforms appear to be differentially involved in the pathogenesis of various diseases. The purpose of this study was to generate monoclonal antibodies (mAbs) specific to different adiponectin isoforms and investigate whether these mAbs have potential as therapeutic agents for such diseases. METHODS: Hybridoma cells producing monoclonal antibodies were generated and screened using enzyme-linked immunosorbent assay and Western blotting for the production of mAbs recognizing human adiponectin isoforms. RESULTS: The mAb from hybridoma clone KH7-41 recognized both the middle molecular weight (MMW) (hexamer) and low molecular weight (LMW) (trimer) isoforms of adiponectin in human serum, whereas the KH7-33 mAb detected only MMW (hexamer) adiponectin. The KH4-8 clone recognized both the high molecular weight (HMW) (multimer) and MMW adiponectin isoforms. However, in mouse and rat sera, the abovementioned antibodies recognized only the MMW isomer. These mAbs also recognized adiponectin in various human tissues, such as lung, kidney, and adipose tissues, although the three mAbs had different staining intensities. The mAb from clone KH4-8 effectively inhibited increases in interleukin-6 (IL-6) and IL-8 expression in recombinant adiponectin-stimulated human osteoblasts and human umbilical vein endothelial cells. Also, the mAbs KH7-33 and KH4-8 significantly ameliorated rheumatic symptoms in a collagen-induced arthritis mouse model. This result suggests that these mAb treatments may ameliorate adiponectin-mediated inflammatory response. CONCLUSIONS: mAbs against human adiponectin isomers can potentially be developed as therapeutic antibodies to target specific detrimental isoforms of adiponectin while maintaining the functions of beneficial isoforms.

An Investigation on the Therapeutic Effect of Thymosin ß4 and Its Expression Levels in Streptozotocin-Induced Diabetic Mice.

Thymosin ß4 (Tß4) treatment was known to show the potential therapeutic effects on diabetic complications. This study was performed to determine if Tß4 expression is changed in both serum and tissues under diabetic conditions and can be a serum biomarker. Type 1 diabetic mice were induced in C57/BL6J mice by intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg body weight. The mice were sacrificed at 16 weeks after STZ injection. Tissues and plasmas were obtained to determine the expression levels of Tß4 using ELISA, real time RT-PCR, and immunohistochemistry. The average serum glucose level was increased to approximately 400 mg/dL beginning 2 weeks after the five injections of STZ and lasting for at least 13 weeks until sacrifice. The plasma and tissue levels of Tß4 in the age-matched control mice were not significantly different from those of the diabetic mice. In conclusion, the Tß4 expression level in the plasmas and tissues of diabetic mice was not affected by diabetic conditions. It indirectly suggests that the therapeutic effect of Tß4 on diabetic complications is due to its regenerative effects on damaged tissue but not to the changed expression level of Tß4 in plasma and tissues of diabetes.

Hypocomplementemic Urticarial Vasculitis Syndrome with Membranous Nephropathy: Case Report.

Urticarial vasculitis is a rare disorder that principally manifests with recurrent urticarial, sometimes hemorrhagic, skin lesions and/or angioedema. Its clinical presentation is not always limited to cutaneous lesions and it can potentially affect other organs, such as the joints, lungs, kidneys, and eyes. Systemic involvement can either be present at the onset of disease or develop over time. In cases with systemic manifestations, urticarial vasculitis is more likely to be associated with a low complement level. We present the case of a teenage boy with hypocomplementemic urticarial vasculitis syndrome (HUVS) that occurred shortly following swine-origin influenza A virus infection in 2009. Afterwards, HUVS was systemically complicated with myositis and membranous nephropathy that developed several months and about 2 years after its onset, respectively. A combination of glucocorticoid and immunosuppressive agents has been used to effectively control disease activity.

Thymosin ß4 in rheumatoid arthritis: Friend or foe.

Rheumatoid arthritis (RA) has characteristic pannus tissues, which show tumor-like growth of the synovium through chronic joint inflammation. The synovium is highly penetrated by various immune cells, and the synovial lining becomes hyperplastic due to increased numbers of macrophage-like and fibroblast-like synoviocytes. Thus, a resultant hypoxic condition stimulates the expression of inflammation-related genes in various cells, in particular, vascular endothelial growth factor. Thymosin ß4 (Tß4), a 5-kDa protein, is known to play a significant role in various biological activities, such as actin sequestering, cell motility, migration, inflammation, and damage repair. Recent studies have provided evidence that Tß4 may have a role in RA pathogenesis. The Tß4 level has been shown to increase significantly in the joint fluid and serum of RA patients. However, whether Tß4 stimulates or inhibits activation of RA immune responses remains to be determined. In the present study, we discuss the logical and clinical justifications for Tß4 as a potential target for RA therapeutics.

Complete Remission of Nephrotic Syndrome Without Resolution of Amyloid Deposit After Anti-Tumor Necrosis Factor α Therapy in a Patient With Ankylosing Spondylitis.

In secondary amyloid A amyloidosis resulting from rheumatologic diseases, tumor necrosis factor α blockers have been reported to be effective in the treatment of both arthritis and amyloidosis. However, there have been few reports concerning the alterations of renal tissue histology before and after long-term tumor necrosis factor α blockers therapy in secondary renal amyloidosis. We report the histological change after tumor necrosis factor α blocker therapy in patient with amyloid A amyloidosis and nephrotic syndrome secondary to underlying ankylosing spondylitis. The patient achieved complete remission of nephrotic syndrome after 17 months of etanercept treatment. We performed the second kidney biopsy after 40 months, and there was little change in the degree of amyloid deposition in the mesangial area and capillary loops compared with the first biopsy. The interstitial inflammation and foot process effacement, however, were fully recovered.

Increased expression of endocan in arthritic synovial tissues: effects of adiponectin on the expression of endocan in fibroblast-like synoviocytes.

This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, was increased in rheumatoid arthritic tissues. In addition, the involvement of adiponectin in the regulation of endocan expression in arthritic joints was examined. Arthritic synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) were immunostained with antibodies to endocan and vascular endothelial growth factor (VEGF). Subsequently, synovial cells and human umbilical vein endothelial cells were cultured and stimulated with interleukin-1 ß (IL-1ß) or adiponectin. The mRNA and protein levels of endocan were evaluated by polymerase chain reaction and ELISA, respectively. Endocan expression was markedly increased in the inflammatory sites of RA synovial tissues. In OA tissues, endocan expression was higher in tissues displaying moderate and severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1ß stimulation. Adiponectin was a more potent stimulant of endocan than IL-1ß at their respective physiological concentrations in synovial cells. Endocan silencing by small interfering RNA transfection of synovial cells decreased in vitro cell migration and invasion. In conclusion, adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints.