[show abstract][hide abstract] ABSTRACT: This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 μg ml(-1)) or IL-1β (0.1 ng ml(-1)) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1β. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1β-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1β. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1β in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.
[show abstract][hide abstract] ABSTRACT: Type 1 myotonic dystrophy (DM1) is an autosomal-dominant inherited disorder with a multisystem involvement, caused by an abnormal expansion of the CTG sequence of the dystrophic myotonia protein kinase (DMPK) gene. DM1 is a variable multisystem disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being reported. But, Electrolytes imbalance is a very rare condition in patients with DM1 yet. Herein we present a 42-yr-old Korean male of DM1 with abnormally elevated serum sodium and potassium. The patient had minimum volume of maximally concentrated urine without water loss. It was only cured by normal saline hydration. The cause of hypernatremia was considered by primary hypodipsia. Hyperkalemic conditions such as renal failure, pseudohyperkalemia, cortisol deficiency and hyperkalemic periodic paralysis were excluded. Further endocrine evaluation suggested selective hyperreninemic hypoaldosteronism as a cause of hyperkalemia.
Journal of Korean medical science 07/2013; 28(7):1111-3. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated whether taurine chloramine (TauCl), which is -endogenously produced by immune cells such as macrophages that infiltrate adipose tissue, affects the differentiation of preadipocytes into adipocytes or modulates the expression of adipokines in adipocytes. To study the physiological effects of TauCl on human adipocyte differentiation and adipokine expression, preadipocytes were cultured under differentiation conditions for 14 days in the presence or the absence of TauCl. Differentiated adipocytes were also treated with TauCl in the presence or the absence of IL-1β (1 ng/ml) for 7 days. The culture supernatants were analyzed for adipokines such as adiponectin, leptin, IL-6, and IL-8. At concentrations of 400-600 μM, TauCl significantly inhibited the differentiation of human preadipocytes into adipocytes in a dose-dependent manner. It did not induce the dedifferentiation of adipocytes or inhibit fat accumulation in adipocytes. Expression of major transcription factors of adipogenesis and adipocyte marker genes was decreased after treatment with TauCl, in agreement with its inhibition of -differentiation. These results suggest that TauCl may inhibit the differentiation of -preadipocytes into adipocytes. Thus, TauCl or more stable derivatives of TauCl could potentially be a safe drug therapy for obesity-related diseases.
Advances in experimental medicine and biology 01/2013; 775:247-57. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily involving the spine and sacroiliac joint and rarely the kidneys. This study aimed to define the clinical and histological features and biology of renal disease in AS. We reviewed the medical records of 681 patients diagnosed with AS from November 2008 to November 2009. Baseline characteristics and laboratory and urinalysis results were reviewed. We identified patients with proteinuria or hematuria and analyzed their risk factors. After providing informed consent, 6 patients underwent a renal biopsy to determine the cause of proteinuria or hematuria. Of the 681 enrolled patients, 547 were men and 134 were women; 81 % were HLA B27 positive, and 8 % had abnormal urinalysis findings (proteinuria, 5.9 %; hematuria, 2.8 %; both, 0.7 %). Incidences of peripheral arthritis and uveitis were 29 % and 18.6 %, respectively. Immunoglobulin (Ig)A and uric acid levels were significantly different between patients with and without proteinuria. Erythrocyte sedimentation rate (ESR), total cholesterol, creatinine, and C-reactive protein (CRP) levels were not statistically significantly different between the 2 groups nor were there any significant differences in IgA, uric acid, ESR, total cholesterol, creatinine, and CRP levels between patients with and without hematuria. Six patients who had >1 g/day proteinuria underwent a renal biopsy; 2 were diagnosed with IgA nephropathy, 1 with amyloidosis, and 3 with non-specific glomerulonephropathy. In the amyloidosis patient, severe proteinuria was the dominant feature. For patients with renal amyloidosis and other forms of glomerulonephritis who initially had normal creatinine levels, tumor necrosis factor (TNF)-alpha blocker therapy resolved proteinuria, but this was not the case for patients with initial renal insufficiency. Renal involvement is not a rare complication of AS, and prognoses differ depending on kidney pathology. Serum levels of uric acid and IgA may predict renal involvement in AS. In cases where abnormal urine sediment is identified, renal biopsy is required to determine prognosis and decide the treatment protocol. Baseline serum creatinine level is important for predicting treatment response.
Rheumatology International 12/2012; · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: IntroductionWhiplash-associated disorder (WAD) is a general after-effect of motor vehicle collisions or sporting accidents. Acupuncture is a common intervention for pain conditions such as musculoskeletal disease. We conducted a pilot trial to determine the efficacy and safety of acupuncture for patients with WAD.MethodologyForty participants were randomly allocated to an acupuncture group or a waiting-list group. The acupuncture group received acupuncture treatment three times per week for 2 weeks.Symptoms were evaluated before random allocation and after 2 weeks. The primary outcome measure was pain intensity. Secondary outcome measures were the SF-36, cervical range of motion (ROM), Self-Rating Depression Scale (SDS), and the Cornell Medical Index (CMI).ResultsThe results demonstrated that the change in visual analogue scale (VAS) in the acupuncture group was −1.85 [−2.67 to −1.02], compared to −0.40 in the waiting-list group [95% CI: −1.18 to 0.38] (p = 0.001). VAS significantly improved from 4.59 [3.67–5.48] at baseline to 2.74 [2.08–3.37] at the endpoint (p < 0.001) in the acupuncture group. No significant changes in secondary outcomes such as SF-36, Cervical ROM, SDS and CMI within either group were observed, and the scores from baseline revealed no significant differences between the groups. There were no reports of serious adverse events related to acupuncture treatment.Conclusions
Acupuncture treatment was associated with a significant alleviation of pain. This pilot study provided preliminary data on the efficacy and safety of acupuncture treatment for WAD. A full-scale randomized controlled trial is required to provide firm evidence of the effectiveness of this intervention.
European Journal of Integrative Medicine 06/2012; 4(2):e151–e158. · 0.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.
Experimental and Molecular Medicine 05/2012; 44(7):440-7. · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was conducted to determine the early cardiac valvular changes in young male ankylosing spondylitis (AS) patients.
A total of 70 AS patients on treatment without clinical cardiac symptoms were divided into group I (< 10 years, n = 50) and group II (≥ 10 years, n = 20) depending on their disease duration after first diagnosis. Twenty-five healthy volunteers were selected as control subjects. All the subjects underwent transthoracic and transesophageal echocardiography, electrocardiography, and rheumatologic evaluation for AS patients.
The thickness of both the aortic and mitral valve was more increased in AS patients than in controls. Aortic valve thickness over 1.3 mm could predict AS with a sensitivity of 73% and specificity of 76%. The prevalence of aortic valve thickening was higher in the AS group compared to the controls. The prevalence of aortic and mitral regurgitation was very low and there was no difference between the controls and the patients. The aortic valve thickening was related to longer disease duration, high blood pressure, disease activity and inflammatory markers.
Thickening of the aortic and mitral valve was observed without regurgitation in male AS patients early in the course of their disease without clinical cardiac manifestations. This subclinical change of aorto-mitral valve in early AS should be considered and followed up to determine its prognostic implication and evolution.
Journal of cardiovascular ultrasound 03/2012; 20(1):30-6.
[show abstract][hide abstract] ABSTRACT: Diabetes mellitus (DM) is a chronic metabolic disease and is associated with vascular complications. However, the association of musculoskeletal manifestations and DM is not clear. We investigated musculoskeletal manifestations in the diabetic animal model Otsuka Long-Evans Tokushima Fatty (OLETF) rat. OLETF rats and control LETO (Long-Evans Tokushima Otsuka) rats at two different ages (44 and 95 weeks) were used. Knee joints and ankles with interphalangeal joints were removed, dissected, stained with hematoxylin and eosin (H&E), periodic acid-Schiff, methenamine silver, and Masson-trichrome staining and examined under light microscopy. Mild degenerative changes with focal edema and mild fibrosis were noted in OLETF rats (at 95 weeks of age) and in age-matched LETO rats, particularly in the interphalangeal joints. Necrosis, phagocytosis of necrotic fibers, regeneration, mononuclear inflammatory cell infiltration, granulation tissue, calcification and cartilage erosion were not observed in either the aged diabetic or the non-diabetic group. We found no prominent musculoskeletal manifestations in the OLETF rats. The reasons may be due to the low prevalence rate of these anomalies, or the life span of rats may be too short to express these alterations. More studies are needed to elucidate the pathophysiological mechanisms by demonstrating the musculoskeletal manifestations histologically.
Molecular Medicine Reports 12/2011; 5(3):779-82. · 1.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: To further understand the expression regulation of MMP-1 and MMP-13 under physiological and pathological conditions, we investigated the combined effects of hypoxia and pro-inflammatory stimuli on the expression of MMP-1 and MMP-13 in rheumatoid synovial fibroblasts.
Synovial fibroblasts were cultured under either hypoxic or normoxic conditions in the presence of IL-1β stimulation. The culture supernatant was analysed for secreted levels of VEGF, MMP-1 and MMP-13. Their gene expression was quantified with real-time and semi-quantitative PCR. Another group of cells was transfected with small-interfering RNA (siRNA) specific for hypoxia-inducible factor-1 α (HIF-1α). The protein levels of HIF-1α were detected by western blot analysis.
In response to 10 ng/ml of IL-1β under normoxia, the levels of MMP-1 and MMP-13 increased compared with the levels observed under hypoxia. IL-1β stimulation under hypoxia induced a 2-fold increase in the level of MMP-1 and a 2-fold decrease in the level of MMP-13 compared with cells cultured under normoxia. A similar pattern of differential expression for MMP-1 and MMP-13 was observed with 1 and 5 ng/ml IL-1β, but not at 0.1 ng/ml. The differential expression of MMPs under the combined effect of IL-1β and hypoxia was significantly attenuated by silencing HIF-1α with siRNA.
Hypoxia in arthritic joints may differentially affect the IL-1β-stimulated expression of MMP-1 and MMP-13 in rheumatoid synovial fibroblasts. This effect is dependent on HIF-1α expression. This hypoxia-mediated differential effect should be taken into consideration when testing the efficiency of therapies that target HIF-1α.
[show abstract][hide abstract] ABSTRACT: This study was performed to provide evidence, albeit indirectly, as to which matrix metalloproteinases (MMPs), among the gelatinases MMP-2 and MMP-9 and the collagenases MMP-1 and MMP-13, play a more proactive role in the angiogenic process in arthritic joint. Joint fluid was collected from 33 patients with rhuematoid arthritis (RA) and osteoarthritis (OA), and protein (MMPs and vascular endothelial growth factor (VEGF)) levels were measured by ELISA, and the association of MMPs with VEGF was evaluated in joint fluid of patients with RA or OA. The levels of collagenases (total MMP-1 and total MMP-13) and gelatinases (total MMP-2 and total MMP-9) in RA joint fluid were significantly higher than those in OA fluid. Total MMP-9 levels were significantly associated with VEGF levels in RA fluids, but not in OA fluid, while total MMP-13 levels were strongly associated with VEGF levels in both RA and OA fluid. However, total MMP-2 and total MMP-1 levels were not associated with VEGF levels in either RA or OA joint fluid. Our results indirectly suggest that in RA and OA, MMP-9 and MMP-13 may play a more important role in angiogenesis than MMP-2 and MMP-1.
Rheumatology International 04/2011; 31(4):543-7. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tumor necrosis factor (TNF)-alpha is a pro-inflammatory cytokine that plays an important role in the pathogenesis of a variety of autoimmune diseases. TNF-alpha inhibitors have been shown to offer clinical benefits in the treatment of autoimmune and inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis (AS), and Crohn's disease. Occasionally, these agents have been associated with infectious complications because of their immunosuppressive activity. Globally, several cases of infections associated with TNF-alpha inhibitors have been reported. However, Aspergillus infection associated with etanercept is very rare. We report a case of chronic necrotizing pulmonary aspergillosis in a 51-year-old man with AS that developed after treatment with etanercept.
International Journal of Rheumatic Diseases 08/2010; 13(3):e16-9. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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).
Synovial cells from RA patients were treated with adiponectin or interleukin (IL)-1beta for 24 hours. The culture supernatant was collected and analyzed for the levels of IL-6, IL-8, prostaglandin E2 (PGE2), 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.
Adiponectin at the concentration of 10 microg/mL stimulated the production of IL-6, IL-8, and PGE2 in RA fibroblast-like synoviocytes (FLSs), although the level of these was much lower than with 1 ng/mL IL-1beta. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1beta. 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.
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.
Arthritis research & therapy 11/2009; 11(6):R161. · 4.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mizoribine is a disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of rheumatoid arthritis. However, clinical use of the drug is restricted to a few Asian countries due to a lack of comprehensive evidence on its effectiveness. The inhibitory effect of the drug on human osteoclastogenesis was investigated in the hopes of providing some clear evidence. Mizoribine was found to inhibit in vitro osteoclastogenesis in a dose-dependent manner. In addition, the size of the pit area was closely related to the number of osteoclasts in a bone resorption assay. However, mizoribine did not affect the phosphorylation of MAP kinase (p38, JNK, ERK), the degradation of IkappaBalpha, or receptor activator of NF-kappaB ligand (RANKL) expression in fibroblast-like synoviocytes stimulated with IL-1beta. These results suggested that mizoribine may partially suppress osteoclastogenesis, leading to progressive bone erosion by inhibiting the growth or the signaling pathway of precursor cells to form osteoclasts rather than fibroblast-like synoviocytes.
European journal of pharmacology 02/2009; 605(1-3):46-8. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tumor necrosis factor (TNF) is a central regulator of chronic inflammatory diseases and plays a major role in the host immune system against tuberculosis (TB). TNF antagonists, infliximab and etanercept are effective in treating chronic inflammatory diseases by inhibiting TNF, but increase the risk of TB as a result of immunosuppression. Previous studies have shown that the risk of TB is greater in patients who received infliximab than in those who received etanercept and several hypotheses on the action mechanisms of the two agents have been presented in order to explain this difference in the risk of TB. As the clinical use of TNF antagonists increase, the incidence rate of TB may increase. Therefore, it is necessary that clinicians considering the use of TNF antagonists pay much attention to the prevention and control of TB and understand the mechanisms of action of the TNF antagonists. This case shows that etanercept treatment can be safely administered during the treatment of TB. In the future, additional studies will be needed to determine the safety of etanercept and the optimal time for the administration of etanercept during the TB treatment.
Rheumatology International 02/2009; 29(11):1377-80. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Post-pregnancy osteoporosis is not a common disease and is hard to diagnosis because their specific situation is post-partum
and lactation. It commonly occurs on lumbar spine within a few months after the birth of a patient’s first child and it could
lead to be fracture after minor trauma. Although its etiology is not clear, it would not be of sufficient magnitude to cause
fractures unless the woman already had a substantial decrease in bone mass. Also, it is rare to be combined with ankylosing
spondylitis. Ankylosing spondylitis has a higher risk of osteoporosis and vertebral fracture which increased with the duration
of disease. We report a case of post-pregnancy osteoporosis with multiple spinal compression fracture in association of ankylosing
Rheumatology International 01/2009; 29(11):1359-1362. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was performed to investigate the frequency of human leukocyte antigen (HLA)-B27 subtypes in the Korean population with spondyloarthropathy (SpA). We determined the HLA subtypes of 267 SpA patients who were positive for the B27 antigen (as determined by serology) by using a PEL-FREEZ kit (Dynal Biotech, Wisconsin, USA). Clinical features, including sex, peripheral joint involvement, and the presence of uveitis, were analyzed in a retrospective cohort study. Among 267 patients, 244 were B*2705-positive and 22 were B*2704-positive. One patient was positive for B*2704/2705. No other subtype was observed among the analyzed patients. We found that HLA-B*2705 was the predominant subtype in Koreans with SpA; this finding is remarkable because other Asians such as the Han or the Japanese exclusively have the B*2704 subtype. This result suggests that the clinical features and prevalence of SpA in Koreans may be similar to those observed in Europeans.
Rheumatology International 06/2008; 29(1):43-6. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Specific antagonists of tumor necrosis factor (TNFalpha) have rapidly gain popularity for the treatment of ankylosing spondylitis (AS). The dose of etanercept has not been determined in Asia, especially in Korea. This study was designed to investigate the maintaining effect of low-dose (25 mg/week) etanercept in Korean patients with AS and after discontinuation, the duration to be aggravated. Patients who had active AS [Bath AS Disease Activity Index (BASDAI) > or =4] were treated with 50 mg of etanercept per week for 3 months. After that, for 6 months, the patients were treated with 25 mg of etanercept per week. We evaluated the serum erythrocyte sediment rate (ESR), C-reactive protein (CRP), and BASDAI every 1 month for 3 months and every 2-3 months during the remaining 6 months. After all schedules of treatment were finished, we reevaluated ESR, CRP, and BASDAI every 4 months until recurrence. Twenty-seven AS patients received etanercept. Twenty-three patients completed treatment for 3 months with a dose of 50 mg/week. Among them, 18 completed for 6 months with a dose of 25 mg/week and discontinued. Mean age was 30.0 +/- 5.4 years and mean disease duration was 7.5 +/- 6.5 years. These 18 patients were evaluated for BASDAI, ESR, and CRP every 4 weeks. After discontinuation, mean duration to recur was 9.2 +/- 6.1 weeks. Twenty-five milligrams of etanercept per week is effective enough to maintain remission in AS. After discontinuation, this effect was maintained by using a dose of 50 mg of etanercept per week.
[show abstract][hide abstract] ABSTRACT: This study was performed to investigate whether synovial proliferation (SP) differentially affects hypoxia in the joint cavities of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Thirty RA and 42 OA patients who underwent synovitis assessment were classified into two groups based on the presence or absence of SP, as revealed by musculoskeletal ultrasonography. Synovial fluids (SFs) from the knee joints were analyzed for interleukin (IL)-8, pO(2), and white blood cell counts and blood samples were analyzed for erythrocyte sedimentation rate (ESR). No difference was found between the OA patients with and without SP in terms of SF oxygen tension (SF pO(2)) or IL-8 level, whereas the RA patients had significantly lower SF pO(2) levels in their knee joints than did the OA patients with SP, and the RA patients had higher levels of IL-8 in their joints than did the OA patients. The counts of infiltrated immune cells in the SF and tissues were much higher for patients with RA and SP than for those with OA and SP. The ESRs were not found to be correlated with SP in OA patients but were negatively correlated with SF pO(2) levels in RA patients. We conclude that ultrasonographically detected SP in OA patients does not generate a more hypoxic SF than that found in OA patients without SP. The SFs from RA patients with SP are hypoxic, which indicates that SP may have different impacts on hypoxia in the joint cavities of RA and OA patients.