| Project/Area Number |
12470432
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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 |
Surgical dentistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
TEI Kanchu Hokkaido Univ., Dent. Hospital, Lec., 医学部・歯学部附属病院, 講師 (80180066)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Yoshitaka Hokkaido Univ., Grad School of Dent., Med. Inst., 大学院・歯学研究科, 助手 (30230816)
DEYAMA Yoshiaki Hokkaido Univ., Grad School of Dent., Asso. Prof., 大学院・歯学研究科, 助教授 (80271667)
SHINDOH Masanobu Hokkaido Univ., Grad. School of Dent., Asso. Prof., 大学院・歯学研究科, 助教授 (20162802)
TOTSUKA Yasunori Hokkaido Univ., Grad. School of Dent., Med. Prof., 大学院・歯学研究科, 教授 (00109456)
DOMON Takanori Hokkaido Univ., Grad. School of Dent., Med. Inst., 大学院・歯学研究科, 助手 (50217618)
長谷川 智一 北海道大学, 大学院・歯学研究科, 助手 (50274668)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | Oral cancer / Bone invasion / Co-culture / Osteoclast / Osteoblast / Interleukin / ODF / RANKL / OPG / OCIF |
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| Research Abstract |
Objectives; Osteoclastic bone resorption is an important step in bone invasion in oral squamous cell carcinomas (SCC). Although several cytokines accelerates osteoclastic bone resorption, it remains unclear whether oral SCC conditioned media may be involved in osteoclastogenesis.
Methods: The co-culture system using osteoblasts and bone marrow cells was performed to examine the activity of osteoclastogenesis by oral cancer cells. Conditioned medium (CM) from oral cancer cells and/or anti-interleukin-6 (IL-6) antibody were added into co-culture. We then used a neutralizing anti-body against osteoclast differentiation factor (ODF)/receptor activator of nuclear factor-kB ligand (RANKL) to determine whether ODF/RANKL produced by osteoblasts in response to CM from oral cancer cells plays a role in the regulation of osteoclastic bone resorption. RT-PCR was performed to assess mRNA expression in osteoblasts.
Results: In co-culture system, CM derived from BHY, a bone-invasive oral cancer cell line, induced tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells. CM from BHY markedly enhanced ODF/RANKL mRNA expression in osteoblastic MC3T3-E1 cells in dose and time dependent manner. The induction of osteoclasts was significantly suppressed when anti-IL-6 antibody was added into the co-culture. Furthermore, treatment with anti-ODF/RANKL antibody almost completely inhibited osteoclastogenesis in co-cuture.
Conclusion: These results strongly suggest that oral cancer cells induce osteoclast generation with paracrine mechanism independent of cell-ceil contact, specifically upregulating ODF/RANKL expression in osteoblasts.
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