Study on the roles of dendritic cells in inflammatory bone destruction

• Project/Area Number: 18592047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Showa University
• Principal Investigator: TAKAMI Masainichi Showa University, School of Dentistry, Lecturer (80307058)
• Co-Investigator(Kenkyū-buntansha): KAMIJO Ryutaro Showa University, School ofDentistry, Professor (70233939) ; YAMADA Atsushi Showa University, School of Dentistry, Lecturer (50407558) ; SUZAWA Tetsuo Showa University, School of Dentistry, Lecturer (60271285) ; MIYAMOTO Yoichi Showa University, School of Dentistry, Associate Professor (20295132)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Bone metabolism / Innate immunity / Osteoclasts / Transcription factor / Gene expression / Cellular differentiation / Dendritic cells / Teeth / 免疫 / 骨破壊 / 遺伝子 / 炎症

Research Abstract

Severe bone destruction is often induced by enhanced osteoclast formation under the inflammatory conditions. Therefore, elucidation of the mechanism of osteoclastogenesis will contribute to the development of methods for the treatment of diseases that accompanies bone destruction. Monocytes and macrophages are known to differentiate into not only osteoclasts but also dendritic cells that play roles of immune responses. We analyzed the changes of cellular characteristics during osteoclastogenesis and dendritic cell differentiation from common precursors. It was found that the potential of dendritic cell differentiation was lost within 24h after beginning of osteoclastogenesis. The characteristics of these cells are quite unique because the cells possessed phagocytic function as well as macrophages but they required RANKL stimulation to survive like osteoclasts. Furthermore, we analyzed mRNA expressions during osteoclastogenesis and dendritic cell differentiation using DNA microarray technique. A transcription factor, IRF-8 was found to be downregulated during osteoclastogenesis but not in dendritic cell differentiation. The IRF-8 deficient mice exerted severe osteoporosis due to enhanced osteoclastogenesis. Moreover, over-expression of IRF-8 in osteoclast precursors strongly suppressed osteoclastogenesis but not dendritic cell differentiation. These results suggest that IRF-8 plays roles of suppression of osteoclastogenesis but not dendritic cell differentiation. These findings will contribute to establishment of new methods for the treatment of periodontal diseases and rheumatoid arthritis.

Research Products

• [Journal Article] Characterization of synovial cell clones isolated from rheumatoid arthritis patients:possible involvement of TNF-α in reduction of osteoprotegerin in synovium (2007)
  • Author(s): Zhao, B., Takami, M., Miyamoto, Y., Suzawa, T., Yamada, A., Mochizuki, A., Yasuhara, R., Wang, X., Namiki, M., Sakamoto, K., Kamijo, R.
  • Journal Title: Cytokine 41 Pages: 61-70
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity (2007)
  • Author(s): Irie, A., Takami, M., Kubo, H., Sekino-Suzuki, N., Kasahara, K., Sanai, Y.
  • Journal Title: Bone 41 Pages: 165-174
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] TGF-β suppresses POEM expression through ERK1/2 and JNK in osteoblasts (2007)
  • Author(s): Miyazono, A., Yamada, A., Morimura, N., Takami, M., Suzuki, D., Kobayashi, M., Tezuka, K., Yamamoto, M., Kamijo, R.
  • Journal Title: FEBS Letter 581 Pages: 5321-5326
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Characterization of synovial cell clones isolated from rheumatoid arthritis patients : possible involvement of TNF-a in reduction of osteoprotegerin in synovium (2007)
  • Author(s): Zhao, B., Takami, M., Miyamoto, Y., Suzawa, T., Yamada, A., Mochizuki, A., Yasuhara, R., Wang, X., Namiki, M., Sakamoto, K., Kamijo, R
  • Journal Title: Cytokine 41 Pages: 61-70
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity (2007)
  • Author(s): Irie, A., Takami, M., Kubo, H., Sekino-Suzuki, N., Kasahara, K., Sanai, Y
  • Journal Title: Bone 41 Pages: 165-174
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] TGF-β suppresses POEM expression through ERK1/2 and JNK in osteoblasts (2007)
  • Author(s): Miyazono, A., Yamada, A., Morimura, N., Takami, M., Suzuki, D., Kobayashi, M., Tezuka, K., Yamamoto, M., Kamijo, R
  • Journal Title: FEBS Lett 681 Pages: 5321-5326
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Interleukin-4 inhibition of osteoclast differentiation is stronger than that of Interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts (2007)
  • Author(s): Yamada, A., Takami, M., Yasuhara, R., Zhao, B., Mochizuki, A., Miyamoto, Y., Eto, T., Yasuda, H., Nakamichi, Y., Kim, N., Katagiri, T., Suda, T., Kamijo, R
  • Journal Title: Immunology 120 Pages: 573-579
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of two biologically-crucial hydroxygroups of(-)-epigallocatechin gallate in osteoclast culture (2007)
  • Author(s): Nakagawa, H., Hasumi, K., Takami, M., Aida-Hyugaji, S., Woo, J-T., Nagai, K., Ishikawa, T., Wachi, M
  • Journal Title: Biochem Pharmacol 73 Pages: 34-43
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nitric Oxide in Pulp Cell Growth, Differentiation and Mineralization (2007)
  • Author(s): Yasuhara, R., Suzawa, T., Miyamoto, Y., Wang, X., Takami, M., Yamada, A., Kamijo, R
  • Journal Title: JDent Res 86(2) Pages: 163-168
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of synovial cell clones isolated from rheumatoid arthritis patients:possible involvement ofTNF-a in reduction ofosteoprotegerin in synovium (2007)
  • Author(s): Zhao, B., Takami, M., Miyamoto, Y., Suzanwa, T., Yamada, A., Mochizuki, A., Yasuhara, R., Wang, X., Namiki, M., Sakamoto, K., Kamijo, R.
  • Journal Title: Cytokine 41 Pages: 61-70
  • Peer Reviewed
• [Journal Article] TGF-β suppresses POEM expression through ERKI/2 and JNK in osteoblasts (2007)
  • Author(s): Micazono, A., Yamada, A., Morimura, N., Takami. M., Suzuki, D., Kobayashi, M., Tezuka, K., Yamamoto, M., Kamijo, R.
  • Journal Title: FEBS Lett. 581 Pages: 5321-5326
  • Peer Reviewed
• [Journal Article] Identification of two biologically-crucial hydroxygroups of (-)-epigallocatechin gallate in osteoclast culture. (2007)
  • Author(s): Nakagawa, H.
  • Journal Title: Biochem Pharmacol 73 Pages: 34-43
• [Journal Article] Nitric Oxide in Pulp Cell Growth, Differentiation and Mineralization. (2007)
  • Author(s): Yasuhara, R.
  • Journal Title: J Dent Res 86・2 Pages: 163-168
• [Journal Article] Identification and Characterization of the Precursors Committed to Osteoclasts Induced by TRANCE/RANKL. (2006)
  • Author(s): Mochizuki, A.
  • Journal Title: J Immunol 177 Pages: 4360-4368
• [Journal Article] Differentiation of osteoclats and dendritic cells from common precursors : relationships between bone metabolism and immune system. (2006)
  • Author(s): Takami, M.
  • Journal Title: Biolog Mechanism Tooth Eruption, Resorption, and Movement 1 Pages: 143-149
• [Journal Article] 破骨細胞の機能と分化 : 細胞に見る免疫と骨代謝の接点 (2006)
  • Author(s): 高見正道
  • Journal Title: 埼玉医科大学雑誌 33・3,4 Pages: 80-81
• [Journal Article] ビタミンD : 炎症・免疫 (2006)
  • Author(s): 高見正道
  • Journal Title: THE BONE 20・6 Pages: 57-61
• [Presentation] Toll-like receptors and Osteoimmunology (2007)
  • Author(s): Masamichi Takami
  • Organizer: 韓国薬学会 シンポジウム
  • Place of Presentation: 韓国 ソウル
  • Year and Date: 2007-11-07
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Toll-like receptors and Osteoimmunology (2007)
  • Author(s): Masamichi Takami
  • Organizer: 韓国薬学会シンポジゥム
  • Place of Presentation: 韓国ソウル
  • Year and Date: 2007-11-07
• [Presentation] Symposium : "Toll-like receptors and Osteoimmunology"
  • Author(s): Masamichi, Takami
  • Organizer: Pharmaceutical Society of Korea
  • Place of Presentation: Seoul, Korea
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Transcription factor IRF-8 is a negative regulator of osteoclast differentiation in vitro and in vivo
  • Author(s): B., Zhao, M., Takami, R., Kamijo, et. al.
  • Organizer: 29th Annual Meeting of the American Society foi Bone and Mineral Research
  • Place of Presentation: Hawaii, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] TGF-beta suppresses POEM expression in osteoblasts
  • Author(s): A., Miyazono, A., Yamada, M., Takami, et. al.
  • Organizer: 29th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Hawaii, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Lysine-specific Gingipain(Kgp) and lipopolysaccharide(LPS) synergistically induces osteoclast differentiation
  • Author(s): R., Yasuhara, Y., Miyamoto, M., Takami, et. al.
  • Organizer: 29th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Hawaii, USA
  • Description: 「研究成果報告書概要(欧文)」より