| Project/Area Number |
15109010
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (S)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
TAKIGAWA Masaharu Okayama University, Grand. Sch. Med. Dent. & Pharm. Sci, Prof (20112063)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Satoshi Okayama Univ., Grad. Sch. Med. Dent. & Pharm. Sci, Assoc. Prof (90221936)
HATTORI Takako Okayama Univ., Grad. Sch. Med. Dent. & Pharm. Sci, Assist. Prof (00228488)
NISHIDA Takashi Okayama Univ., Grad. Sch. Med. Dent. & Pharm. Sci, Assist. Prof (30322233)
YAMAMOTO Teruko Tohoku University, Graduate School of Dentistry, Professor (00127250)
TABATA Yasuhiko Kyoto University, Institute for Frontier Medical Sciences, Professor (50211371)
青山 絵理子 岡山大学, 歯学部, 教務員 (10432650)
山合 友一朗 岡山大学, 大学院医歯薬学総合研究科, 助手 (00158057)
椋代 義樹 岡山大学, 歯学部, 教務員 (50325099)
小守 壽文 長崎大学, 医歯薬学総合研究科, 教授 (00252677)
中西 徹 岡山大学, 大学院・医歯学総合研究科, 助教授 (30243463)
|
|---|
| Project Period (FY) |
2003 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥103,870,000 (Direct Cost: ¥79,900,000、Indirect Cost: ¥23,970,000)
Fiscal Year 2006: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Fiscal Year 2005: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2004: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2003: ¥27,690,000 (Direct Cost: ¥21,300,000、Indirect Cost: ¥6,390,000)
|
|---|
| Keywords | CTGF / CCN2 / regeneration / regenerin / hard tissue / binding molecule / regulation of gene expression / signal transduction / mutant animal / 間葉系幹細胞 / 血管 / 受容体 / 遺伝子発現 / 歯根膜 / 結合蛋白 / CCN22 / CCNファミリー / 骨 / 軟骨 / 骨髄間葉系幹細胞 / 結合組織成長因子(CTGF) / CTGF遺伝子ノックアウトマウス / ゼラチンハイドロゲル |
|---|
| Research Abstract |
1. Using wild type and/or mutant animals, we found that in addition to endochondral ossification in growth plate, CTGF/CCN2 was involved in secondary ossification center formation, intramembranous ossification, formation of periodontal ligament and articular and auricular cartilages, distraction osteogenesis and repair of tooth extraction socket. In vivo administration of CTGF/CCN2 with gelatin hydrogel into the artificial defect of articular cartilage and bone resulted in repair of these tissues, respectively. Taken together with the finding that platelets contained much CTGF/CCN2, these findings indicate that CTGF/CCN2 functions as a regeneration factor "regenerin".
2. We developed CTGF/CCN2 domain-specific antibodies and domain-specific ELISA systems. The function and signal transduction pathway of each domain was different depending on types of cells, such as chondrocytes and endothelial cells. CT domain of CTGF/CCN2 promoted adhesion of mesenchymal stem cells on hydroxyapatite plates, suggesting a possible application for bone regeneration with a combination of CTGF/CCN2 and hydroxyapatite.
3. A cis-element in 3'-untranslation region (3'-UTR) of CTGF/CCN2 mRNA, which was involved in destabilization of its mRNA, and a protein, which bound to the element, were found in chondrocytes. The biding between them changed in reverse relation to the process of chondrocyte differentiation. A hypoxia-inducible protein, which stabilized CTGF/CCN2 mRNA by binding to its 3'-UTR was also detected.
4. CTGF/CCN2 bound to perlecan, aggrecan and fibronectin, indicating its retention in extracellular matrix. CTGF/CCN2 had collaborative action with M-CSF on cartilage. Low density lipoprotein-related protein I was one of the receptors for CTGF/CCN2 in chondrocytes. Concerning signal transduction pathway of CTGF/CCN2 in chondrocytes, PKC was found as an upstream mediator of ERK and p38MAPK. JNK was involved in cell proliferation. PI3K and PKB were found to be involved in calcification.
|
