The practice of anti-cytokine treatment for temporomandibular joint osteoarthritis
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants |
|Research Institution||Okayama University |
UEHARA Junji University hospital of Medicine and Dentistry, Research Assistant, 医学部・歯学部附属病院, 助手 (10379836)
KUBOKI Takuo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (00225195)
FUJISAWA Takuo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Research Assistant, 大学院医歯薬学総合研究科, 助手 (20325096)
MINAKUCHI Hajime Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Research Assistant, 大学院医歯薬学総合研究科, 助手 (30325097)
|Project Period (FY)
2005 – 2006
Completed (Fiscal Year 2006)
|Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
|Keywords||osteoarthritis of TMJ / type II soluble tumor necrosis factor / etanercept / anti cytokine therapy / joint injection therapy / 可溶型腫瘍壊死因子受容体 / 完全ヒト型可溶性TNFα / LTαレセプター製剤 / エンブレル【○!R】|
We examined in vitro and in vivo for achievement of "The practice of anti-cytokine treatment for temporomandibular joint osteoarthritis".
Confluent cultured cells of rat primary articular chondrocytes were stimulated with TNFα, IL-1β or both cytokines for 24 hours. The anti-TNFα biological drug (etanercept) was added after stimulation with cytokines 6 and18 hours later. The gene expressions of mmp3, 9 and 13 in chondrocytes were evaluated by real-time RT-PCR.
1) Compared with control condition, cytokine stimulation significantly up-regulate the gene expression of each mmps at 24h. Under both cytokines stimulation condition, the gene expression of each mmps was more up-regulation than under TNFα or IL-1β stimulation condition.
2) Etanercept addition inhibited the up-regulation of mmp3, 9 and 13 gene expressions under TNFα or both cytokines stimulation condition. But each mmps gene expressions were not inhibited by etanercept at any time points under IL-1β stimulation condition.
3) The up-re
gulation of the gene expression of mmp3 or mmp9 stimulated by TNFα was significantly inhibited by etanercept at 24 h, at 12 and 24 h, respectively.
Etanercept was injected into the knee joint of the monoiodoacetic acid (MIA) induced experimental rat osteoarthritis model to histologically evaluate the effect on inhibition of damaged cartilage.
1) All of rats injected etanercept were not inhibited their articular cartilage damage.
These results indicated that etanercept had the inhibitory effect on the expression of MMP3, 9 and 13 induced TNFα in OA-like condition. Though mmp3, 9 and 13 gene expressions were not inhibited in the IL-1β addition, each mmps gene expressions were inhibited by etanercept in the both TNFα and IL-1β addition. Therefore it may be hopeful that etanercept is effective on the treatment of osteoarthritis with severe inflammation such as synovial tissue inflammation. Unfortunately the effectiveness of etanercept was not positive in vivo. We should evaluate the validity of this investigation in the future study.
In this investigation, we could not achieve the final objective of "The practice of anti-cytokine treatment for temporomandibular joint osteoarthritis". But present results are needful data for us to accomplish the purpose of this study. Less
Report (3 results)
Research Products (12 results)