| Project/Area Number |
11470400
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | KANAGAWA DENTAL COLLEGE |
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Principal Investigator |
KUBOTA Eiro KANAGAWA DENTAL Co., Second Dept. of Oral Maxillofacial Surgery, Professor, 歯学部, 教授 (50170030)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Masaru KANAGAWA DENTAL Co., Second Dept. of Oral Maxillofacial Surgery, Assistant Professor, 歯学部, 講師 (00162024)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | TMD / Synovial fluid analysis / Proinflammatory cytokine / Proteinases / Free radicals / Cartilage degradation / 蛋白分解酵素 |
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| Research Abstract |
We have shown that several types of matrix metalloproteinases MMPs with different substrate specificities were detectable in synovial fluid(SF) from patients who suffered from temporomandibular disorders(TMD). Among these MMPs, existence of MMP-1,2,3, and 9 were correlated to bone morphologic changes of the TMJ. Our deta have also shown that induction of the active-form of MMP9 and MMP3 was important for cartilage degradation in TMJ with internal derangement(ID), which further proceeds to osteoarthritis. To further test the hypothesis that TMJ chondrocytes and disc cells synthesize specific MMPs in vitro upon cytokine stimulation, we isolated these cells from IL-1-injected rat TMJs. MMP9 and MMP3 syntheses were inducible in these cells by IL-1, whereas MMP2 was constitutively expressed on both cell types. Our studies also demonstrated that pro-forms of MMP9 and MMP3 were converted into their active-forms in vitro by IL-1 stimulation, whereas IL-1 had no remarkable effect on expression of inhibitors of MMPs(TIMPs). These results indicate that MMP9 and MMP3 are predominantly produced by disc cells and chondrocytes, and the activation of the MMPs may be regulated by proinflammatory cytokines(IL-1 and/or TNFα). These findings also suggest that IL-1 or TNFα, which usually exists in SF of patients with ID or OA, may have important roles in synthesis and activation of ECM-degrading proteinases, thereby exacerbating cartilage breakdown.
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