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

  • Moon, Su-Jin (Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Jeong, Jeong-Hee (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Jhun, Joo Yeon (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Yang, Eun Ji (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Min, Jun-Ki (Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Choi, Jong Young (Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Cho, Mi-La (The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea)
  • Received : 2013.12.02
  • Accepted : 2014.02.20
  • Published : 2014.02.28
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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-$1{\beta}$ (IL-$1{\beta}$), 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-$1{\beta}$, 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-$1{\beta}$-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.

Keywords

References

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