Current studies have revealed the capacity of mesenchymal stem cells (MSCs) in term of immunomodulatory properties, and this distinct potential is downgraded according to the disease duration of patients-derived MSCs. In order to enhance the immunomodulatory and anti-tumorigenic properties of the rheumatoid arthritis (RA) joints-derived MSCs, we aggregate synovial fluid-derived MSCs from RA joints (RA-hMSCs) into 3D-spheroids by the use of hanging drop culture method. Cells were isolated from synovial fluids of RA joints with longstanding active status over 13 years. For aggregation of RA-hMSCs into 3D-spheroids, cells were plated in hanging drops in 30 μL of advanced DMEM (ADMEM) containing 25,000-30,000 cells/ drop and cultured for 48 h. To analyze the comparative immunomodulatory effects of 3D-spheroid and 2D monolayer cultured RA-hMSCs and then cells were cultured in ADMEM supplemented with 20% of synovial fluids of RA patients for 48 h and were evaluated by qRT-PCR for their expression of mRNA levels of inflammatory and antiinflammatory markers. Cellular aggregation of RA-hMSCs was observed and cells were aggregate into a single sphere. Following treatment of RA patient’s synovial fluids into the RA-hMSCs, spheroids formed RA-hMSCs showed significantly (p < 0.05) higher expression of TNFα stimulated gene/protein 6 (TSG-6) than the monolayer cultured RAhMSCs. Therefore, the 3D-spheroid culture methods of RA-hMSCs were more effective than 2D monolayer cultures in suppressing inflammatory response treated with 20% of RA-synovial fluids by expression of TNFα (TSG-6) according to the immune response and enhanced secretion of inflammatory factors.

본 연구는 CIA에 의해 유발된 DBA/1 마우스를 통해 류마티스관절염 바이오마커에 대한 두 충 추출물의 효과를 평가하였다. 평가를 위해 류마티스관절염 동물모델 제작 후 100 ㎎/㎏/day로 4주간 경구 투여하고 혈청 바이오마커, 방사선, 구조적 매개변수 분석을 통해 치료 효과를 확인하였다. 음성대 조군과 비교하여, 두충 추출물은 염증 및 면역글로불린 마커(TNF-α, IgG 및 hs-CRP)의 생성을 유의 하게 감소시켰고, 백혈구의 단핵구 수를 유의적으로 감소시켰다. 또한, 두충 추출물은 관절 파괴를 효과 적으로 보존하고 관절 변형을 줄였으며, 골 밀도의 증가와 유의적으로 골 염증을 감소시켰다. 이러한 결 과는 두충 추출물이 류마티스관절염 증상을 개선하는 것을 나타낸다. 따라서, 두충 추출물은 류마티스관 절염 관리를 위한 새로운 치료 옵션이 될 수 있음을 보여준다.

본 연구는 CIA로 유도된 류마티스 관절염 모델에서 지골피 추출물이 류마티스관절염 관련 인자에 미치는 영향을 평가하였다. 동물 모델에 류마티스관절염을 유발한 후 지골피 추출물을 4주간 200 ㎎/㎏/day 용량으로 경구 투여하였다. 이후 혈액, 방사선 및 조직 분석에 기초하여 효과를 평가하였다. 그 결과, 대조군에 비해 지골피 추출물은 사이토카인, 케모카인 및 면역글로불린 생성을 유의하게 감소시켰다. 또한, 지골피 추출물은 중족골을 효과적으로 보존하였으며, H&E 및 M&T 염색에서도 대조군에 비해 조직 병리학적 개선이 있음을 보여주었다. 이와 같은 결과는 지골피 추출물이 류마티스관절염 증상을 완화시켰음을 나타내고 있다. 따라서 지골피 추출물은 류마티스 관절염 관리를 위한 새로운 치료옵션이 될 수 있다.

Calcineurin-binding protein 1 (Cabin1) regulates calcineurin phosphatase activity as well as the activation, apoptosis, and inflammatory responses of fibroblast-like synoviocytes (FLSs), which actively participate in the chronic inflammatory responses in rheumatoid arthritis (RA). However, the mechanism of action of Cabin1 in FLS apoptosis is not clear. The aim of this study was to define the regulatory role of Cabin1 in FLSs of mice with collagen-induced arthritis (CIA). Transgenic mice overexpressing human Cabin1 in joint tissues, under the control of a type II collagen promoter, were generated. hCabin1 expression in joints and FLSs was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of cytokines, matrix metalloproteinases (MMPs), and apoptosis-related genes in FLSs was determined by enzyme- linked immunosorbent assay, gelatin zymography, and RT-PCR, respectively. Joints were histologically examined after H&E and TRAP staining. hCabin1-transgenic CIA mice had less severe arthritis than wild-type CIA mice, based on hind paw thickness and histology. This was accompanied by significantly enhanced apoptosis in transgenic mice, evidenced by significantly more TUNEL-positive cells in synovial tissues. The expression of inflammatory cytokines and MMPs was reduced, and the transgenic CIA mice exhibited decreased Akt activation and increased expression of p53, caspase-3, caspase-9, and Bax. hCabin1 plays a critical role in promoting apoptosis of FLSs and in attenuating inflammation and the destruction of cartilage and bone in RA. These findings help elucidate the pathogenic mechanisms of RA and suggest that Cabin1 is a potential target for RA treatment.

alcineurin (CN) is a calcium and calmodulin-depedent serine/threonine phosphatase. CN plays an important role in various biological processes including cell proliferation, cardiovascular, skeletal muscle development and apoptosis. In rheumatoid arthritis (RA), CN plays a role synoviocyte activation and arthritis progression. The selective inhibition of CN by the over-expression of CN-binding protein 1 (Cabin1). In the present study, joint restricted transgenic mice expressing the human Cabin1(hCabin1) were generated, driven by type II collagen promoter and efficiency of these mice was investigated by experimental arthritis. These transgenic mice successfully expressed hCabin1 in joint tissue as well as other organs like the liver, the heart, and the brain. The joint specific over-expression of hCabin1 reduced the disease severity during collagen-induced arthritis. In fibroblast-like synoviocytes (FLSs) from hCabin1 transgenic mice, the productions of these cytokines including, TNF-α, IL-1β and IL-6 were decreased and MMPs was also depressed in transgenic mice FLS. In addition, the expression of proapoptotic p53, p21, caspase-3, caspase-9 and Bax increased in transgenic mice, indicating that hCabin1 may induce FLS death by regulating the expression of Bcl-2, p53, p21, caspase-3, casepase-9 and Bax. It is expected that these findings will provide a more knowledge about the pathogenic mechanisms of rheumatoid arthritis and a potential animal model of the choronic inflammatory conditions, including atherosclerosis and transplantation.

Arthritis is a common disease in aged people, and is clinically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Although common symptoms such as pain are present, the underlying pathological mechanisms are slightly different. Therefore, the objectives of the present study were to compare joint damage induced by RA and OA by analyzing the major morphological and molecular differences, and to propose a suitable therapeutic intervention based on the pathophysiological conditions of bones and joints. For the RA animal model, 8-week-old DBA1/J mice were immunized with bovine type II collagen emulsified in complete Freund’s adjuvant (CFA). Normal C57BL/6 mice (over 2 years of age) were used for OA. The clinical arthritis score was calculated using a subjective scoring system, and paw thicknesses were measured using calipers. The serum TNFα level was analyzed using an ELISA kit. Micro- CT was used to identify pathological characteristics and morphological changes. In collagen-induced RA mice, there were increased ankle joint volumes and clinical scores (p<0.01). The concentration of TNFα was significantly increased from 3 to 7 weeks after immunization. Micro-CT images showed trabecular bone destruction, pannus formation, and subchondral region destruction in RA mice. OA among aged mice showed narrowed joint spaces and breakdown of articular cartilage. This study suggests that a careful therapeutic intervention between RA and OA is required, and it should be based on morphological alteration of bone and joint.

Arthritis may well be the diagnosis most commonly encountered by physicla therapists. Until the past few year, physical therapy treatment programs for arthritis consisting of heat, ROM, isometric exercise and rest were the rule. But now physical therapy treatment activities have changee. New philosophies, about exercise in particular, have emerge, as well as an improved understanding and application of physical agents. Therefore a review of the literature regarding physical therapy for rheumatoid arthritis is presented.

Background: Taraxacum platycarpum has been used in traditional medicine in Korea to treat intoxication and edema and as a diuretic. According to previous reports, it has anti-cancer, anti-gastritis, and anti-inflammation effects. However, the improvement effect of T. platycarpum on rheumatoid arthritis has not been investigated. The anti-oxidative and anti-inflammation effects of the aerial parts of T. platycarpum are different from those of its subterranean parts. Thus, we evaluated the effect of the water extracts of Taraxaci radix (WTR) on type II collagen-induced rheumatoid arthritis (CIA) in animal models. Methods and Results: Rheumatoid arthritis was induced by type II collagen. WTR (100㎎/㎏ and 500㎎/㎏) was administered to the animal models. Methotrexate was used as the positive control. The levels of interleukin-6, TNF-alpha, and type II collagen IgG in the animals were measured by using enzyme-linked immunosorbent assay. Treatment with 500㎎/㎏ WTR decreased the serum levels of interleukin-6, TNF-alpha, and collagen IgG in the CIA models. Moreover, treatment with WTR diminished the arthritisinduced swelling of the hind legs and monocyte infiltration in the bloodvessels of the animal models. Conclusions: These results indicate that WTR has the potential to improve rheumatoid arthritis by reducing the levels of inflammatory cytokines such as interleukin-6 and TNF-alpha. However, further experiments are required to elucidate the influence of WTR on signal transduction in vitro and in vivo.

Due to the thick cortical structure, subtrochanteric fractures of femur is often caused by high energy trauma and there are only a few report of it from low energy trauma. We have experienced a case of bilateral subtrochanteric fracture which oc-curred after a simple slip down. The fracture was healed with applying intramedullary nail. We believe the fracture may have occurred from prolonged use of steroid which was used to treat underlying rheumatoid arthritis.

Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Gastroenteritis was the most frequent clinical sign and osteoarticular infection like septic arthritis were extremely scarce in a patient with Salmonella infection. An immunocompromised state are known risk factors for development of septic arthritis due to Salmonella. The treatment of rheumatoid arthritis (RA) has recently seen a paradigm shift with the introduction of biological therapy. Tumor necrosis factor-alpha antagonist (anti TNF-α) have especially been able to play major roles in the treatment of RA. But there is concern that this will result in an increased incidence of infection. There have been few reports of Salmonella infection following anti TNF-α in a RA patient. Here, we report a rare case of septic arthritis of the left knee by Group B non-typhoidal Salmonella in a RA patient who was receiving etanercept therapy. The patients was treated with arthroscopy guided irrigation and debridement, and administration of intravenous antibiotics (ciprofloxacin) for 4 weeks. Since then, he achieved a full recovery from the infection.