ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 34

Rebamipide Attenuates Pain Severity and Cartilage Degeneration in a Rat Model of Osteoarthritis by Downregulating Oxidative Damage and Catabolic Activity in Chondrocytes

Su-Jin Moon1, Mi-La Cho2, Yeon-Sik Hong3, Sung-Hwan Park4 and Jun-Ki Min1, 1Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul, South Korea, 2Rheumatism Research Center, Catholic Research Institute of Medical Science, Catholic University of Korea, Seoul, South Korea, 3Our Lady of Mercy Hospital, Inchon, South Africa, 4Catholic University of Korea, Seoul, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Biology and Pathology of Bone and Joint

Session Type: Abstract Submissions (ACR)

Background/Purpose: The development and progression of osteoarthritis (OA) are now believed to involve inflammation, even in the early stage of disease. Proinflammatory cytokines and chemokines are critical mediators of the disturbed homeostasis in the OA cartilage matrix. Also, OA is associated with oxidative stress. Excessive production of oxidants has been linked with apoptosis of cartilage chondrocytes both in vitro and in vivo. Rebamipide, a gastroprotective agent, exhibits an anti-inflammatory and radical-scavenging property. We investigated the effects of rebamipide on pain generation, cartilage destruction, and various indicators of local oxidative damage and inflammatory status in a monosodium iodoacetate (MIA)-induced OA rat model, 

Methods: OA was induced in rats by intra-articular injection of MIA. Oral administration of rebamipide was initiated on the day of MIA injection or 3 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase 13 (MMP-13), interleukin-1β (IL-1β), hypoxia-inducible factor-2α (HIF-2α), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes.

Results: Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1ß, HIF-2a, iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1ß-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase -1 and -3.

Conclusion: The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.

Disclosure:

S. J. Moon,
None;

M. L. Cho,
None;

Y. S. Hong,
None;

S. H. Park,
None;

J. K. Min,
None.

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/rebamipide-attenuates-pain-severity-and-cartilage-degeneration-in-a-rat-model-of-osteoarthritis-by-downregulating-oxidative-damage-and-catabolic-activity-in-chondrocytes/