| 1.Research Institution | Tokyo Medical and Dental University | |
| 2.Research Area | Integrated Fields | |
| 3.Research Field | Tissue Engineering | |
| 4.Term of Project | FY1996〜FY2000 | |
| 5.Project Number | 96I00205 | |
| 6.Title of Project | Tissue Engineering for Hard Tissues |
| Name | Institution,Department | Title of Position |
| Shoji Enomoto | Tokyo Med&Dent. Univ. Oral Surgery | Professor |
8.Core Members
| Names | Institution,Department | Title of Position |
| Isao Ishikawa | Tokyo Med&Dent. Univ Periodontics | Professor |
| Kenichi Shinomiya | Tokyo Med&Dent. Univ Orthopaedics | Professor |
| Masaki Noda | Tokyo Med&Dent. Univ Molecular Pharmacology | Professor |
9.Cooperating Researchers
| Names | Institution,Department | Title of Position |
| Izumi Asahina | Tokyo Med&Dent. Univ Oral Surgery | Assist Professor |
| Soichiro Ito | Tokyo Med&Dent. Univ Orthopaedics | Assist Professor |
| Shigeru Oda | Tokyo Med&Dent. Univ Periodontics | Assist Professor |
10.Summary of Research Results
|
Bone Morphogenetic Protein (BMP) has been expected to be utilized for the repair of bone defects because of its bone inductive activity. We have already confirmed that the implantation of BMP with a carrier regenerate the bone defects in rats and dogs. Whereas, contrary to our expectation, the graft of BMP alone did not reconstruct the mandibular bone defects in primates, which were closer species to humans. One of the reasons for the discrepancy in these results may be a lower response of the cells to BMP due to aging. However, we found that the combination graft of BMP and bone marrow, or culture expanded osteoprogenitor cells, reconstructed mandibular bones in primates This method is a reliable way to regenerate bony defects. The carriers of BMP play important role in BMP-inducing bone formation. Therefore, we tried to develop new carriers of BMP and we confirmed that PLLA sponge and biphasic calcium phosphate worked well as the carriers. Additionally, we developed a new artificial bone substitute, a collagen/hydroxyapatite composite. The material was strong enough to support the stress loading, and it had a direct bond to bone and is gradually substituted by the newly formed bone. Furthermore, we found that this new material was a good carrier of BMP. To understand the fundamental mechanism of bone formation, we analyzed the mRNA expression of Cbfa1, a transcriptional factor, concerned to bone formation. We found that Cbfa1 was expressed constitutionally in osteoblasts and chondrocytes and BMP enhanced its expression. Additionally, we identified several new genes, transcriptional factors related to the differentiation of osteoblast and chondrocyte. These results will lead us to develop new therapy which contribute to patients who suffered from osseous diseases. |
11.Key Words
(1)Bone Morphogenetic protein、(2)Osteoblast, Chondrocyte、(3)Carrier
(4)Tissue Engineering
12.References
| Author | Title of Article | |||
| Yamashita T | Retardation in bone resorption after bone marrow ablation in klotho mutant mice. | |||
| Journal | Volume | Year | Pages Concerned | |
| Endocrinology | 141 | 2000 | 438-445 | |
| Author | Title of Article | |||
| Takazawa Y | CBFA1, IS Constitutively expressed in chondrocytic cell line, TC6, and its expression is upregulated byBMP2. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Endocrinology | 165 | 2000 | 579-586 | |
| Author | Title of Article | |||
| Sekiya I | SOX9 enhances aggrecan gene promoter/enhancer activity and is upregulated by Retinoic Acid in a Cartilage-Derived Cell Line, TC6. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Biological Chemistry | 275 | 2000 | 10738-10744 | |
| Author | Title of Article | |||
| Tsuji K | Identification and Expression of a novel 3'-exon of mouse Runx1/Pebp2 α B/Cbfa2/AML1 gene. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochemical and Biophysical Research Communications | 274 | 2000 | 171-176 | |
| Author | Title of Article | |||
| Kawaguchi N | Mitf is expressed in osteoclast progenitors in vitro. | |||
| Journal | Volume | Year | Pages Concerned | |
| Experimental Cell Research | 260 | 2000 | 284-291 | |
| Author | Title of Article | |||
| Furuya K. | Overexpression of Cas-interactiong zinc finger protein (CIZ) suppresses proliferation and enhances expression of type I collagen gene in osteoblast-like MC3T3E1 cells. | |||
| Journal | Volume | Year | Pages Concerned | |
| Experimental Cell Research | 261 | 2000 | 329-335 | |
| Author | Title of Article | |||
| I Ishikawa | Regeneration of periodontal tissues Now and Future | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Japanese dental medicine | 19 | 2000 | 112-115 | |
| Author | Title of Article | |||
| S Oda, | The effect of EMDOGAIN | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Japanese Dentist | 52 | 2000 | 115 | |
| Author | Title of Article | |||
| A Kinoshita | Regeneration of Periodontal tissues | |||
| Journal | Volume | Year | Pages Concerned | |
| The Journal of Dental Engineering | 134 | 2000 | 9-12 | |
| Author | Title of Article | |||
| Kikuchi M | Self-Organization Mechanism in a Bone-like Hydroxyapatite / Collagen Nanocomposite Synthesized in vitro and Its Biological Reaction in vivo. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biomaterials, | 2000 | in press | ||
| Author | Title of Article | |||
| Kikuchi M | Preparation of Hydroxyapatite / Collagen Composites using Biomimetic Process and Their Biocompatibility. | |||
| Journal | Volume | Year | Pages Concerned | |
| Mater. Res. Soc. Sym. Proc. | 599 | 2000 | 51-53 | |
| Author | Title of Article | |||
| Takakuda K | Bone Reconstruction with Hydroxyapatite / Collagen. | |||
| Journal | Volume | Year | Pages Concerned | |
| Proc. Internat. WS on Bio- integrated Mater. & Tissue Eng. | 2000 | 72-73 | ||
| Author | Title of Article | |||
| Miki T, | Experience with freeze-dried PGLA/HA/rhBMP-2 as a bone graft substitute. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Cranio-Maxillofacial Surgery. | 28 | 2000 | ||
| Author | Title of Article | |||
| Kikuchi M | Hap/Collagen Biomimetic synthesis has bone morphigenetic ability | |||
| Journal | Volume | Year | Pages Concerned | |
| Intelligent Materials | 10 | 2000 | 14-18 | |
| Author | Title of Article | |||
| Manabe A | Pateulized autogenous bone graft for reconstruction after resection of osteosarcoma | |||
| Journal | Volume | Year | Pages Concerned | |
| Orthopaedic Surgery and Traumatology | 43 | 2000 | 1089-1096 | |
| Author | Title of Article | |||
| Seto I | Reconstruction of Primate Mandible by the Combination graft of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) and Bone Marrow. | |||
| Journal | Volume | Year | Pages Concerned | |
| American Journal of Oral and Maxillofacial Surgery. | 59 | 2001 | 53-61 | |
| Author | Title of Article | |||
| Md. Imranul Alam | Comparative study of biphasic calcium phosphate ceramics impregnated with rhBMP-2 as bone substitutes. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Biomedical Materials Research | 54 | 2001 | 129-138 | |
| Author | Title of Article | |||
| Md. Imranul Alam | Evaluation of ceramics composed of different hydroxyapatite to tricalcium phosphate ratios as carriers for rhBMP-2 | |||
| Journal | Volume | Year | Pages Concerned | |
| Biomaterials | 2001 | |||
| Author | Title of Article | |||
| Moriyama T | Development of cultured oral mucosa utilizing collagen sponge matrix and contracted collagen gel A preliminary study for clinical applications | |||
| Journal | Volume | Year | Pages Concerned | |
| Tissue Engineering | 2001 | in press | ||
| Author | Title of Article | |||
| Md. Imranul Alam | Prefabricated vascularized bone flap: a tissue transformation technique for bone reconstruction. | |||
| Journal | Volume | Year | Pages Concerned | |
| Plastic and Reconstructive Surgery. | 2001 | in press | ||
| Author | Title of Article | |||
| Yonezawa H | Effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) on Distraction Osteogenesis:An Experimental Study in Rabbit Mandible. | |||
| Journal | Volume | Year | Pages Concerned | |
| The Asian Jounal of Oral and Maxillofacial Surgery. | 2001 | 81-90 | ||
| Author | Title of Article | |||
| Ishii Y | Experimental Study of Secondary Bone Graft of Alveolar Clefts using Bone Morphogenetic Protein (BMP). | |||
| Journal | Volume | Year | Pages Concerned | |
| The Journal of the Stomatological Society, Japan. | 68,1 | 2001 | 111-124 | |
| Author | Title of Article | |||
| Oda M | Prefabrication of vascularized bone flap using bone morphogenetic protein | |||
| Journal | Volume | Year | Pages Concerned | |
| The Journal of the Stomatological Society, Japan. | 68,1 | 2001 | in press | |
| Author | Title of Article | |||
| Itoh S | Enhancement of bone ingrowth in a titanium fiber mesh implant by rhBMP-2 and hyaluronic acid. | |||
| Journal | Volume | Year | Pages Concerned | |
| J Materials Science: Materials in Medicine | 2001 | in press | ||
| Author | Title of Article | |||
| Itoh S | The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2. | |||
| Journal | Volume | Year | Pages Concerned | |
| J Biomedical Materials Research | 54 | 2001 | 445-453 | |
| Author | Title of Article | |||
| Itoh S | A study on induction of nerve regeneration using bioabsorbable tubes. | |||
| Journal | Volume | Year | Pages Concerned | |
| J reconstr microsurg | 17(2) | 2001 | in press | |
| Author | Title of Article | |||
| Kuroda K | Improvement autogenous bone graft for reconstruction after resection of osetosarcoma | |||
| Journal | Volume | Year | Pages Concerned | |
| J. East. Jpn. Orthop. Traumatol | 13 | 2001 | in press | |
| Author | Title of Article | |||
| Itoh S | Investigation of Collagen cross link technique | |||
| Journal | Volume | Year | Pages Concerned | |
| Microsurgery | 14(1) | 2001 | in press | |
| Author | Title of Article | |||
| Kawaguchi N | Spontaneous mutation in Mitf gene causes osteopetrosis in silver homozygote quail. | |||
| Journal | Volume | Year | Pages Concerned | |
| Developmental Dynamics | 2001 | in press | ||
| Author | Title of Article | |||
| Nemoto H | Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Bone and Mineral Research. | 16 | 2001 | in press | |
| Author | Title of Article | |||
| Asou Y | Osteopontin facilitates angiogenesis, accumulation of osteoclasts and resorption in ectopic bone. | |||
| Journal | Volume | Year | Pages Concerned | |
| Endocrinology | 142 | 2001 | in press | |
| Author | Title of Article | |||
| Yamashita T | Klotho-deficient mice are resistant to bone loss induced by unloading due to sciatic neurectomy | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Endocrinology | 168 | 2001 | in press | |
| Author | Title of Article | |||
| Ishijima M | Enhancement Of Osteoclastic Bone Resorption And Supression Of Osteoblastic Bone Formation In Response To Reduced Mechanical Stress Do Not Occur In The Absence Of Osteopontin. | |||
| Journal | Volume | Year | Pages Concerned | |
| The Journal Of Experimental Medicine | 193 | 2001 | 399-404 | |
| Author | Title of Article | |||
| Ihara H | Parathyroid hormone-induced bone resorption does not occur in the absence of osteopontin. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Biological Chemistry | 2001 | in press | ||
| Author | Title of Article | |||
| Tsuji K | Transient Suppression of Cbfal Expression by Basic Fibroblast Growth Factor (bFGF) in Rat Osteoblast-like Osteosarcoma ROS17/2.8 Cells. | |||
| Journal | Volume | Year | Pages Concerned | |
| Journal of Bone and Mineral Metabolism. | 2001 | in press | ||