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KMID : 0923620140140010045
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Immune Network
2014 Volume.14 No. 1 p.45 ~ p.53
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Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats
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Moon Su-Jin
Jeong Jeong-Hee
Jhun Joo-Yeon
Yang Eun-Ji
Min Jun-Ki
Choi Jong-Young
Cho Mi-La
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Abstract
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Osteoarthritis (OA) is a degenerative joint disease charac-terized by a progressive loss of cartilage. And, increased oxi-dative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver dis-eases known for its free radical-scavenging property. The ob-jectives 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 admin-istration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw with-drawal latency and threshold. Samples were analyzed macro-scopically 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 osteo-clasts in subchondral bone legion compared with the ve-hicle-treated OA group. UDCA reduced the expression of IL-1β, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA ex-pression 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 in-duced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting ca-tabolic factors that are implicated in the pathogenesis of car-tilage damage in OA.
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KEYWORD
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Ursodeoxycholic acid (UDCA), Monosodium iodoacetate (MIA), Osteoarthritis, Oxidative stress
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