| Project/Area Number |
15390636
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthodontic/Pediatric dentistry
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY |
|---|
Principal Investigator |
TANNE Kazuo Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30159032)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANIMOTO Kotaro Hiroshima University, Graduate School of Biomedical Sciences, research associate, 大学院・医歯薬学総合研究科, 助手 (20322240)
OHNO Shigeru Hiroshima University, Graduate School of Biomedical Sciences, research associate, 大学院・医歯薬学総合研究科, 助手 (30304447)
HONDA Koubun Hiroshima University, Graduate School of Biomedical Sciences, research associate, 大学院・医歯薬学総合研究科, 助手 (00335663)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥7,400,000 (Direct Cost: ¥7,400,000)
|
|---|
| Keywords | osteoarthritis / low molecular hyaluronan (HA) / synovial membrane cell / mechanical stress / hyaluronidase / chondrocyte / HAoligo / siRNA / 機械的伸長力 / TSG-6 / ITI / CD44 / 抗CD44抗体 / MMP / TIMP |
|---|
| Research Abstract |
To elucidate the mechanism of cartilage degradation and pathologic progress in osteoarthritis (OA), we carried out sequential studies as follows by means of biochemical methods.
In 2003 and 2004, we examined the effects of low molecular weight hyaluronan (HA) on cultured articular chondrocytes and pursued the regulatory method for HA fragmentation. In this study, we clarified that degradation or fragmentation of HA accelerates cartilage degradation with up-regulation of matrix metalloproteinases in articular joints (Ohno-Nakahara M. et al., J.Biochem. 135 : 567-575, 2004 ; Ohno S. et al., Arthritis Rheum. 52 : 800-809, 2005). In addition, we clarified that HAS2, which played a crucial role in production of high molecular weight HA, gene expression was greatly facilitated by acting growth factor such as TGF-β on cultured synovial membrane cells (Tanimoto K. et al., J Dent.Res., 83 : 40-44, 2005).
In 2005, we examined the effects of high magnitude tensile load on HA metabolism in cultured chondrocytes and synovial membrane cells. In this study, we clarified HYAL2 gene expression and HAase activity in cultured synovial membrane cells were enhanced by high magnitude cyclic tensile load. Although HYAL2 gene expression in cultured chondrocytes was also enhanced by tensile load, HAase activity was not changed. In addition, we clarified that HYAL2 siRNA inhibited HAase activity of synovial membrane cells subjected high magnitude tensile load.
These results suggested that HA fragmentation was directly involved in cartilage degradation and the biochemical cause for HA fragmentation was HYAL2 expression induced by high magnitude tensile load. On the other hand, therefore TGF-β induced production of high molecular weight HA, it was strongly suggested that TGF-β was an effective inhibitor of cartilage degradation followed by HA fragmentation.
|
