Rheumatoid Arthritis: Cho YS

Kim HL, Cho YS, Choi H, Chun YS, Lee ZH, Park JW. · Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. · Biochem Biophys Res Commun. · Pubmed #19013431 No free full text.

Abstract: Rheumatoid arthritis (RA) is known to be associated with increased risks of hypoxia-related diseases, whose progresses are critically determined by HIF-1alpha. The authors hypothesized that the hypoxia-related complications of RA are associated with HIF-1alpha deregulation by some factor(s) in RA serum. Arthritis was induced in female Lewis rats by injecting complete Freund's adjuvant. The effects of arthritic rat serum (ARS) on hypoxic responses were investigated by incubating Hep3B cells in ARS. In the presence of ARS, HIF-1alpha was down-regulated and inactivated under hypoxic conditions. ARS inactivated AKT and mTOR, which led to impaired HIF-1alpha protein synthesis. Furthermore, insulin was found to be deficient in ARS and insulin supplementation fully recovered HIF-1alpha synthesis with AKT and mTOR activation. These results suggest that HIF-1alpha deregulation by components in serum is responsible for the RA-associated aggravation of hypoxic diseases in extra-articular tissues.

Lee EY, Lee CK, Lee KU, Park JY, Cho KJ, Cho YS, Lee HR, Moon SH, Moon HB, Yoo B. · Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea. · Rheumatol Int. · Pubmed #16944157 No free full text.

Abstract: OBJECTIVE: To test the ability of alpha-lipoic acid (LA) to attenuate the development of collagen-induced arthritis (CIA) in mice. METHODS: Mice were divided into three groups and treated with intraperitoneal administration of LA (10 or 100 mg/kg) or placebo. Clinical, histologic, and biochemical parameters were assessed. Human synovial fibroblasts and peripheral blood mononuclear cells were cocultured in various concentrations of LA to evaluate the effects on osteoclastogenesis. RESULTS: LA was associated with a dose-dependent reduction of CIA, as well as preventing bone erosion and destructive changes. Intracellular reactive oxygen species in lymphocytes obtained from inguinal lymph nodes, which was significantly higher in CIA than control mice, was significantly reduced in CIA by LA. The concentrations of TNF-alpha, IL-1beta, and IL-6 in the paws, and synovial NF-kappaB binding, all of which were markedly higher in CIA than control mice, were reduced by treatment with LA. In addition, LA inhibited the formation of human osteoclasts in vitro. CONCLUSION: Amelioration of joint disease by LA was associated with reduction in oxidative stress, as well as inhibition of inflammatory cytokine activation and NF-kappaB DNA binding activity. Moreover, LA inhibited bone destruction in vivo and osteoclastogenesis in vitro. Collectively, these results indicate that LA may be a new adjunctive therapy for rheumatoid arthritis.

Lee CK, Lee EY, Cho YS, Moon KA, Yoo B, Moon HB. · Division of Allergy and Rheumatology, Department of Internal Medicine, Asan Institute for Life Science, Seoul, Korea. · Korean J Intern Med. · Pubmed #16134770 links to  free full text

Abstract: BACKGROUND: Glucocorticoids have been known to be less effective for treating ankylosing spondylitis (AS) patients than for treating rheumatoid arthritis (RA) patients. To elucidate the mechanisms underlying this phenomenon, we evaluated whether the glucocorticoid receptor (GR) beta expression of the peripheral blood mononuclear cells (PBMCs) in patients with AS is increased compared with patients with RA. METHODS: PBMCs were isolated from the subjects of 3 study groups: the healthy controls (n=25), the RA patients (n=25), and the AS patients (n=25). All the subjects had never taken corticosteroids and the patients with RA or AS were newly diagnosed. The expression of GR beta messenger RNA (mRNA) was determined by reverse transcription of the total RNA, and this was followed by semi-quantitative polymerase chain reaction analysis (RT-PCR). RESULTS: The level of GR alpha mRNA expression was not different among three groups. GR beta mRNA expression of the AS patients (2.02 [range: 0.99-7.21], median [25th-75th percentiles]) was enhanced compared with that of the controls (0.78 [range: 0.43-1.62]) and the RA patients (0.98 [range: 0.79-1.18]). The level of GR beta mRNA expression was not related to the inflammatory markers or the disease activity score 28 for the RA patients, and it was not related to the Bath ankylosing spondylitis disease activity index for the AS patients. CONCLUSION: The expression of GR beta mRNA, which is a dominant negative regulator for the glucocorticoid response, was increased in AS patients. The results suggest that the increased expression of GR beta mRNA may be related to the ineffectiveness of glucocorticoids for the treatment of AS.

Kim SH, Lee CK, Lee EY, Park SY, Cho YS, Yoo B, Moon HB. · Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. · Rheumatol Int. · Pubmed #14628150 No free full text.

Abstract: OBJECTIVE: The aim of this study was to measure serum oxidized low-density lipoprotein (Ox-LDL) levels in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and to identify any association with clinical variables. METHODS: We studied 126 female patients (27 with active RA, 27 with inactive RA, 72 with SLE). One hundred fifteen age-matched healthy women (76 for RA, 39 for SLE) with no clinical or laboratory evidence of disease served as normal controls. Serum Ox-LDL levels were measured with a commercial enzyme-linked immunosorbent assay kit (Mercodia, Sweden). RESULTS: The serum Ox-LDL levels were significantly higher in patients with active RA (P<0.05) or SLE (P<0.01) than age-matched controls and significantly higher in patients with active RA than with inactive RA (P<0.01). The levels of serum total cholesterol and LDL were significantly lower in patients with RA than in age-matched controls (P<0.01). There was no correlation among serum Ox-LDL levels and inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) or rheumatoid factors in patients with RA. CONCLUSIONS: Compared with healthy women, those with SLE or active RA had increased serum Ox-LDL levels, which may contribute to the increased risk of cardiovascular disease in this patient group.

Lim MK, Lee CK, Ju YS, Cho YS, Lee MS, Yoo B, Moon HB. · Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. · Rheumatol Int. · Pubmed #11354563 No free full text.

Abstract: To investigate the relationship between serum ferritin and disease activity in systemic lupus erythematosus (SLE), we enrolled 128 patients with SLE (18 males and 110 females). Twenty-eight patients (2 males and 26 females) with rheumatoid arthritis (RA) served as controls. The SLE patients were subdivided into three groups according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores: groups A (0-5), B (6-9), and C (> or =10). We prospectively evaluated 48 SLE patients before and after treatment. Serum ferritin and anti-dsDNA antibody were measured by radioimmunometric assay. C-reactive protein (CRP) was measured quantitatively by immunonephelometry. Complements 3 and 4 (C3 and C4) were measured by nephelometry. Serum levels of ferritin during the more active stage of SLE (group C) exceeded those of RA patients and patients at less active stages of SLE (groups A and B). There were no significant differences between RA patients and groups A and B. Serum ferritin was elevated especially in serositis and hematologic manifestation. In this prospective study, changes in SLEDAI scores before and after treatment correlated significantly with serum ferritin levels and inversely to C3 and C4 levels. We confirm that serum ferritin levels can be a useful marker of disease activity in SLE patients.

Lee CK, Hong JS, Cho YS, Yoo B, Kim GS, Moon HB. · Division of Allergy-Rheumatology, Department of Internal Medicine and Asan Institute for life Science, Seoul, Korea. · J Korean Med Sci. · Pubmed #11306745 links to  free full text

Abstract: We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/- 1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea.