• Journal of Acupuncture Research
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• v.19 no.6
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• pp.155-170
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• 2002

면역억제와 면역항진의 작용을 지닌 녹용(鹿茸)약침의 실험쥐에서의 type II collagen(CII)으로 유발된 관절염(CIA)에 대한 효과를 연구하였다. 본 실험에서 녹용(鹿茸)약침군과 생리식염수군을 대조군으로 하여 실험쥐에게 약침시술을 하였다. 녹용(鹿茸)약침이 CII에 작용하는 세포반응에 대한 효과를 검정하였는데, 대조군에서는 CII 유발주사 후 24일에 관절염이 관찰되었고, CIA의 정도가 점차적으로 심해졌다. 생리식염수 처리군과 비교해 24일 동안 하루에 한번 $50{\mu}g/kg$ 이상 용량의 녹용(鹿茸)약침은 CII 처리 T cell의 interleukin 2(IL-2)와 interferon-${\gamma}$($IFN-{\gamma}$) 생산능력을 억제했다. 또한 녹용(鹿茸)약침은 CII처리 임파절과 대식세포의 tumor necrosis facter ${\alpha}$($TNF-{\alpha}$)의 생산을 억제했다. 한편 CIA에 대한 약침효능의 지표는 녹용(鹿茸)약침을 14일간 하루에 한번씩 처리하면서, 소의 CII로 3주 간격으로 2번 유발접종을 실시하여 검정하였다. 첫 CII 유발접종과 동시에 일일 투여량 $100{\mu}g/kg$으로 14일간의 녹용(鹿茸)약침이 항체형성과 CII에 대한 지연형 과민성 뿐만 아니라 관절염의 증가도 막아주었다. 녹용(鹿茸)약침을 관절염 유발성 CII의 2차 접종과 동시에 시술한 결과, 관절염과 CII에 대한 면역반응을 억제하였다. 이에 저자는 CII로 유발된 관절염에 대한 녹용(鹿茸)약침의 억제효과에 대하여 보고하는 바이다.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1278-1284
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• 2007

Solanum Iyratum Thunb (Solanaceae) has multiple applications in korean traditional medicine because of its cytotoxic, immunological and anti-inflammatory activities. However, no study on the anti-arthritic activity of Solanum Iyratum Thunb has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production were assessed during CIA(collagen-induced arthritis) model mice in lymph node (LN), in knee joint and spleen, using ELISA. DBA/1j mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with Solanum Iyratum Thunb (SLT) orally at 400, 200 mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. SLT significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IFN-gamma in serum and spleen cell culture supernatant. The erosion of cartilage was dramatically reduced in mouse knees after treatment with SLT. In conclusion, our results demonstrates that SLT significantly suppressed the progression of CIA. This action was characterized by suppression of arthritis index, cartilage erosion and synovial cell infiltration and the decreased production of $TNF-{\alpha}$, $IFN-{\gamma}$, CD4+, CD19+, CD3+/CD69+ cells (in lymph node), CD11b+/Gr-1 + (in knee joint).

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.113-118
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• 2008

Temporomandibular joint disorder (TMD) can induce severe pain but, its pathogenic mechanisms remain poorly understood. In this study, we analyzed proteomes of human synovial fluid in the superior joint space in the patients with TMD, which is obtained during the treatment arthrocentesis. We've got this result that one of the spots was consistently down-regulated in synovial fluid of patients with TMD from analysis of protein pattern. Its molecular weight was estimated to be 33 kDa. Synoviolin was identified in our proteomics analysis of LC/MS/MS. This protein was recently reported as one of the proteins that might affect rheumatoid arthritis (RA). Synoviolin that might be associated with RA was detected in synovial fluid of patients with TMD. We can conclude that synoviolin might be involved not only in the pathogenesis of RA but also in TMD. In result, synoviolin might be involved in the pathogenesis of TMD and can be candidates as new therapeutic targets of TMD or early detection biomarkers.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.150-162
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• 2009

Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.

• Journal of Acupuncture Research
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• v.18 no.1
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• pp.113-128
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• 2001

Objective : To investigate the effect of BUM aqua-acupuncture in treating the RA, the immunosis to logical analysis of LPS induced arthritis in mice to study this. For 14th day after the injection of LPS & BUM injection, the distribution of fibroblast, collagen, CD54(ICAM-1), CD106(VCAM-1), IL-$1{\beta}$, IL-2 receptor, CDl lb(macrophage) were examined on synovial capsule of mice knee joint. For 14th day after the injection of LPS & BUM injection, the distribucion of CD4(TH cell), CD8(TC cell), CD40(B cell) were examined on common iliac lymph node in mice. Methods : The experimental model of arthritis was induced by injection of 300${\mu}g$/kg LPS in BALB/c mice weighing 30g. The 100${\mu}l$ BUM aqua-acupuncture which compounded calculus bovis, fel ursi and moschus was injected into GB34 of mice every other day for 12 days. For 3rd, 7th, 14th day after the injection of LPS, the neutrophil, lymphocyte and monocytc counts in WBC were measured using hemacytometer. Results : The obstain results are summarized as follows ; 1. In sample group, the neutrophils counts were increased and the lympnocytes counts were decreased compared with control group. 2. The distribution of fibrosis & fibroblast on synovial membrane were decreased compared with control group. 3. The distribution of collagen fiber on synovial membrane were decreased compared' with control group. 4. The distribution of CD54(ICAM-1) & CD106(VCAM-1) on synovial membrane were decreased compared with control group. 5. The distribution of IL-$1{\beta}$ & IL-2 receptor on synovial membrane were decreased compared with control group. 6. The distribution of CDb(macrophage) on synovial membrane were decreased compared with control group. 7. The distribution of CD4(TH cell), CD8(TC cell) and CD40(B cell) in common iliac lymph nodes were decreased compared with control group. Conclusions : BUM aqua-acupuncture stimulation decreased inflammatory responses LPS induced arthritis in mice.

• YAKHAK HOEJI
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• v.57 no.3
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• pp.161-166
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• 2013

Sinomenium acutum has been used for the treatment of rheumatoid arthritis, arrhythmia, and pain. We evaluated the quality of S. acutum extract by quantitatively analyzing its components such as sinomenine, magnoflorine and syringaresinol with the simultaneous determination method using HPLC-DAD. A total of 53 samples collected from different localities were evaluated with this quality evaluation method. Sinomenine, magnoflorine and syringaresinol from tested samples ranged from 0.0649~9.1050%, 0.7460~10.7590% and 0.0010~0.2441%, respectively. In the current study, we were able to exhibit the diverse quality of S. acutum samples collected from various locations using the simultaneous determination method.

• Biomedical Science Letters
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• v.15 no.1
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• pp.61-66
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• 2009

Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis (RA). Leflunomide known as a regulator of iNOS synthesis which largely decreases NO production in diverse cell type. However, the effect of leflunomide on chondrocyte is still poorly understood. In our previous studies, we have shown that direct production of Nitric oxide (NO) by treating chondrocytes with NO donor, sodium nitroprusside (SNP), causes apoptosis via p38 mitogen-activated protein kinase in association with elevation of p53 protein level, caspase-3 activation. In this study, we characterized the molecular mechanism by which A77 1726 inhibit apoptosis. We found that A77 1726 inhibit NO-induced apoptosis as determined by MTT (Thiazolyl Blue Tetrazolium Bromide) assay and DNA fragmentation. The inhibition of apoptosis by A77 1726 was accompanied by increased PI-3 kinase and AKT activities. So, inhibition of phosphatidylinositol (PI)-3kinase with LY294002 rescued apoptosis. Triciribine, the specific inhibitor of AKT, also abolished anti-apoptotic effect. Our results indicate that A77 1726, the active metabolite of leflunomide, mediates NO-induced apoptosis in chondrocytes by modulating up-regulation of PI-3 kinase and AKT.

• International Journal of Stem Cells
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• v.17 no.1
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• pp.91-98
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• 2024

The development of in vitro models is essential in modern science due to the need for experiments using human material and the reduction in the number of laboratory animals. The complexity of the interactions that occur in living organisms requires improvements in the monolayer cultures. In the work presented here, neuroepithelial stem (NES) cells were differentiated into peripheral-like neurons (PLN) and the phenotype of the cells was confirmed at the genetic and protein levels. Then RNA-seq method was used to investigate how stimulation with pro-inflammatory factors such as LPS and IFN𝛾 affects the expression of genes involved in the immune response in human fibroblast-like synoviocytes (HFLS). HFLS were then cultured on semi-permeable membrane inserts, and after 24 hours of pro-inflammatory stimulation, the levels of cytokines secretion into the medium were checked. Inserts with stimulated HFLS were introduced into the PLN culture, and by measuring secreted ATP, an increase in cell activity was found in the system. The method used mimics the condition that occurs in the joint during inflammation, as observed in the development of diseases such as rheumatoid arthritis (RA) or osteoarthritis (OA). In addition, the system used can be easily modified to simulate the interaction of peripheral neurons with other cell types.

• Molecules and Cells
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• v.37 no.6
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• pp.449-456
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• 2014

The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23b-transfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated1 cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.

• Journal of Life Science
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• v.29 no.8
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• pp.888-894
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• 2019

Cartilage diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA), are associated with the loss of chondrocytes and degradation of articular cartilage. Recent studies revealed that inflammatory reactive oxygen species (ROS) and age-related oxidative stress can affect chondrocyte activity and cartilage homeostasis. We investigated changes in the levels of intracellular antioxidants during cellular senescence of primary chondrocytes from rat articular cartilages. Cellular senescence was induced by serial subculture (passages 0, 2, 4, and 8) of chondrocytes and measured using specific senescence-associated ${\beta}$-galactosidase ($SA-{\beta}-gal$) staining. ROS production increased significantly in the senescent chondrocytes. In addition, total glutathione (GSSG/GSH) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) expression increased in senescent chondrocytes induced by serial subculture. Analysis of changes in intracellular antioxidant levels in articular cartilage from rats of different ages (5, 25, 40, and 72 wk) revealed that total glutathione levels were highest after 40 wk and slightly decreased after 72 wk as compared with those after 25 wk. SOD and HO-1 expression levels increased in accordance with age. Based on these results, we conclude that intracellular antioxidants may be associated with cartilage protection against excessive oxidative stress in the process of chondrocyte senescence and age-related cartilage degeneration in an animal model.