2004 Fiscal Year Final Research Report Summary
Establishment of periodontal tissue engineering by FGF-2
Project/Area Number |
14370709
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Periodontal dentistry
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Research Institution | Osaka University |
Principal Investigator |
MURAKAMI Shinya Osaka University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (70239490)
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Co-Investigator(Kenkyū-buntansha) |
SHIMABUKURO Yoshio Osaka University, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (50231361)
KITAMURA Masahiro Osaka University, Dental Hospital, Assistant Professor, 歯学部附属病院, 講師 (10243247)
YAMADA Satoru Osaka University, Dental Hospital, Assistant Professor, 歯学部附属病院, 講師 (40359849)
SAHO Teruyuki Osaka University, Dental Hospital, Instructor, 歯学部附属病院, 助手 (10263295)
ASANO Taiji Kaken Pharmaceutical Co.Ltd., Senior investigator, 総合研究所, 主任研究員
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Project Period (FY) |
2002 – 2004
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Keywords | periodontal tissue / periodontal tissue regeneration / basic fibroblast growth factor / cytokine therapy / periodontal ligament cell / hyaluronan / PLAP-1 / osteopontin |
Research Abstract |
We investigated the regulatory effects of basic fibrovlast growth factor(bFGF) on the production of various extracellular matrices which play important roles in the regulation of periodontal tissue regeneration and can be candidate(s) of the carrier material(s) of bFGF-containing regenerative medicine. It was demonstrated that bFGF preferentially induced hyaluronan and heparan sulfate production by human periodontal ligament (HPDL) cells in a dose dependent manner. Analysis by HPLC revealed that in conditioned medium of bFGF-treated HPDL cells HA had a higher molecular mass, compared to that of untreated HPDL cells. RT-PCR analysis revealed that the enhancement of mRNA expression of hyaluronan synthase (HAS) 1 and HAS2, both of which contribute to the production of HA with a high molecular mass. In terms of heparan sulfate, the shedding of syndecan-2 of the surfaces of bFGF-treated HPDL cells was observed. The transcriptome analysis of HPDL cells revealed the existence of periodontal ligament associated protein-1 (PLAP-1), novel proteoglycan-like protein. We demonstrated that PLAP-1 negatively regulated the cytodifferentiation of HPDL cells into hard-tissue forming cells and that bFGF downregulated the expression of PLAP-1. In terms of bone-related proteins, bFGF downregulated the expressions of bone sialoprotein, osteonectin and osteocalcin by HPDL cells. Interestingly, however, bFGF clearly enhanced the osteopontin expression at both mRNA and protein levels. The osteopontin was detected in the cytoplasm and the conditioned medium but not on the surfaces of bFGF-treated HPDL cells. Furthermore, it was revealed that ERK1/2 and PKC were involved in the signaling pathway(s) of bFGF-induced osteopontin expression. We are now planning to investigate the efficacy of bFGF plus scaffold material(s) to induce periodontal tissue regeneration by utilizing the severe periodontitis model of beagle dogs.
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Research Products
(14 results)