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      KCI등재 SCOPUS SCIE

      Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

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      https://www.riss.kr/link?id=A103887599

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      다국어 초록 (Multilingual Abstract)

      Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1β, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.
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      Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known ...

      Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1β, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

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      참고문헌 (Reference)

      1 Okada, K., "Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am" 295 : G735-G747, 2008

      2 Poupon, R., "Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action" 36 (36): S3-S12, 2012

      3 Corpechot, C., "The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis" 128 : 297-303, 2005

      4 Kuettner, K. E., "Synthesis of cartilage matrix by mammalian chondrocytes in vitro. I. Isolation, culture characteristics, and morphology" 93 : 743-750, 1982

      5 Scott, J. L., "Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease" 69 : 1502-1510, 2010

      6 Chadjichristos, C., "Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes" 278 : 39762-39772, 2003

      7 Kobayashi, K., "Sodium iodoacetate-induced experimental osteoarthritis and associated pain model in rats" 65 : 1195-1199, 2003

      8 Pelletier, J. P., "Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: possible link with the reduction in chondrocyte apoptosis and caspase 3 level" 43 : 1290-1299, 2000

      9 Chevalier, X., "Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study" 32 : 1317-1323, 2005

      10 Kapoor, M., "Role of proinflammatory cytokines in the pathophysiology of osteoarthritis" 7 : 33-42, 2011

      1 Okada, K., "Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am" 295 : G735-G747, 2008

      2 Poupon, R., "Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action" 36 (36): S3-S12, 2012

      3 Corpechot, C., "The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis" 128 : 297-303, 2005

      4 Kuettner, K. E., "Synthesis of cartilage matrix by mammalian chondrocytes in vitro. I. Isolation, culture characteristics, and morphology" 93 : 743-750, 1982

      5 Scott, J. L., "Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease" 69 : 1502-1510, 2010

      6 Chadjichristos, C., "Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes" 278 : 39762-39772, 2003

      7 Kobayashi, K., "Sodium iodoacetate-induced experimental osteoarthritis and associated pain model in rats" 65 : 1195-1199, 2003

      8 Pelletier, J. P., "Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: possible link with the reduction in chondrocyte apoptosis and caspase 3 level" 43 : 1290-1299, 2000

      9 Chevalier, X., "Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study" 32 : 1317-1323, 2005

      10 Kapoor, M., "Role of proinflammatory cytokines in the pathophysiology of osteoarthritis" 7 : 33-42, 2011

      11 Cotofana, S., "Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI" 21 : 1214-1222, 2013

      12 Najim, R. A., "Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters" 34 : 308-314, 2007

      13 Guzman, R. E., "Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis" 31 : 619-624, 2003

      14 Tiku, M. L., "Malondialdehyde oxidation of cartilage collagen by chondrocytes" 11 : 159-166, 2003

      15 Durigova, M., "MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein" 30 : 145-153, 2011

      16 Dean, D. D., "Levels of metalloproteases and tissue inhibitor of metalloproteases in human osteoarthritic cartilage" 14 (14): 43-44, 1987

      17 Sanghi, D., "Is radiology a determinant of pain, stiffness, and functional disability in knee osteoarthritis? A cross-sectional study" 16 : 719-725, 2011

      18 Sharma, A. R., "Interplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis" 14 : 19805-19830, 2013

      19 Carlo, M. D. Jr., "Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels" 48 : 3419-3430, 2003

      20 Guerne, P. A., "IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro" 144 : 499-505, 1990

      21 Mendes, A. F., "Hydrogen peroxide mediates interleukin-1beta- induced AP-1 activation in articular chondrocytes: implications for the regulation of iNOS expression" 19 : 203-214, 2003

      22 Tanaka, S., "Factors related to degradation of articular cartilage in osteoarthritis: a review" 27 : 392-399, 1998

      23 Tiku, M. L., "Evidence linking chondrocyte lipid peroxidation to cartilage matrix protein degradation. Possible role in cartilage aging and the pathogenesis of osteoarthritis" 275 : 20069-20076, 2000

      24 Ljubuncic, P., "Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages" 39 : 475-478, 1996

      25 Poupon, R. E., "Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis" 113 : 884-890, 1997

      26 Huebner, J. L., "Collagenase 1 and collagenase 3 expression in a guinea pig model of osteoarthritis" 41 : 877-890, 1998

      27 Felson, D. T., "Clinical practice. Osteoarthritis of the knee" 354 : 841-848, 2006

      28 Remans, P. H., "CTLA-4IG suppresses reactive oxygen species by preventing synovial adherent cell-induced inactivation of Rap1, a Ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells" 54 : 3135-3143, 2006

      29 Lapenna, D., "Antioxidant properties of ursodeoxycholic acid" 64 : 1661-1667, 2002

      30 Lukivskaya, O., "Antioxidant mechanism of hepatoprotection by ursodeoxycholic acid in experimental alcoholic steatohepatitis" 51 : 54-59, 2006

      31 Song, R. H., "Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5" 56 : 575-585, 2007

      32 Kim, J., "A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders" 690 : 12-23, 2010

      33 Poupon, R. E., "A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group" 324 : 1548-1554, 1991

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      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2025 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2022-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2021-12-01 평가 등재로 하락 (재인증) KCI등재
      2016-02-22 학회명변경 영문명 : Korean Association Of Immunbiologists -> The Korean Association of Immunologists
      2016-01-01 평가 우수등재학술지 선정 (계속평가)
      2012-01-01 평가 등재 1차 FAIL (등재유지) KCI등재
      2009-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2008-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2007-01-01 평가 등재후보학술지 유지 (등재후보2차) KCI등재후보
      2006-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2004-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.36 0.36 0.29
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.24 0.2 0.636 0
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