Analyses of mechanical stress-induced bone formation and metabolism on aging osteoblasts and osteo-like cells

• Project/Area Number: 19592280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hirosaki University
• Principal Investigator: KUSUMI Akinori Hirosaki University, 大学院・医学研究科, 客員研究員 (90332494)
• Co-Investigator(Kenkyū-buntansha): 楠美 智巳 弘前大学, 大学院医学研究科, 講師 (90322932) ; 佐藤 寿 弘前大学, 医学部附属病院, 助教 (90311539) ; 榊 宏剛 弘前大学, 医学部附属病院, 助教 (90374850)
• Co-Investigator(Renkei-kenkyūsha): 佐藤 寿 弘前大学, 医学部附属病院, 講師 (90311539) ; 榊 宏剛 弘前大学, 医学部附属病院, 助教 (90374850)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 細胞・組織 / 周期的伸展刺激 / 細胞老化 / MAPK / シグナル伝達 / ヒト骨芽細胞 / 細胞継代・細胞老化 / OPG / MAPK活性化 / RANKL / 組織・細胞 / シグナル伝達経路

Research Abstract

申請者らは、一軸方向周期的伸展刺激(以下、伸展刺激)負荷された正常ヒト骨芽細胞のOPG/RANKL 産生制御について報告(Kusumi A. et al.JBMM23.373-381.2005)してきたが、他の報告とOPG/RANKL産生や、活性化するMAPKの経路に違いがあり、この矛盾の解析が急務であった。
そこで、本研究では、購入した正常ヒト骨芽細胞を継代培養してそれぞれの継代細胞に伸展刺激負荷し、第3継代と第5継代の正常ヒト骨芽細胞について比較解析したところ、第3継代では伸展刺激負荷でp38MAPK経路活性化依存性のOPG産生亢進、RANKL産生抑制制御が認められたが、第5継代では伸展刺激負荷でERK1/2活性化し、OPG産生抑制、RANKL mRNA発現亢進となるが、OPG/RANKL産生制御はERK1/2 経路依存性ではなかった。つまり、申請者らの報告と他の報告との違いの重要なポイントは培養継代の影響である事がわかった。更に、骨芽細胞の継代による細胞老化の方向に研究を向けたかったが、老化関連遺伝子発現の変化は認められなかった。

Research Products

• [Journal Article] 鬼島宏関節遊離体の臨床病理 : 離断性骨軟骨炎を中心に (2009)
  • Author(s): 楠美智巳, 津田英一, 石橋恭之, 楠美昭則
  • Journal Title: 病理と臨床 27 Pages: 275-282
• [Journal Article] 関節遊離体の臨床病理 : 離断性骨軟骨炎を中心に (2009)
  • Author(s): 楠美智巳, 他
  • Journal Title: 病理と臨床 27 Pages: 275-282
  • Peer Reviewed
• [Journal Article] Passage.affected competitive regulation of osteogrotegerin synthesis and the receptor activator of nuclear fanor-χ B ligand mRNA expression in normal human osteoblasts stimulated by the application of cyclic tensile strain (2009)
  • Author(s): Kusumi A., et.al.
  • Journal Title: J Bone Minel Metabolism (in press)
  • Peer Reviewed
• [Journal Article] Basic-helix-loop-helix(bHLH)transcription factor DEC2 negatively regulates vascular endothelial growth factore expression (2008)
  • Author(s): Sato F, Bhawal UK, Kawamoto T, FujimotoK, Imaizumi T, Imanaka T, Kondo J, Koyanagi S. Noshiro M. Yoshida H. Kusumi T, Kato Y, Kijima H.
  • Journal Title: Genes Cells 13 Pages: 131-144
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of the carcinoma in the specimen obtained radial prostatectomy following hormone therapy (2008)
  • Author(s): Kusumi T. Koie T, Tanaka M, MatsumotoK, Sato F, Kusumi A, Ohyama C, Kijima H.
  • Journal Title: Pathol Int 58 Pages: 687-691
  • Peer Reviewed
• [Journal Article] In vivo chemotherapeutic profile of human gallbladder small cell carcinoma (2008)
  • Author(s): Nishime C, Ohnishi Y, Suemizu H, Tamaoki N, Kusumi T, Sato F, Yamazaki H, Nakamura M, Ueyama Y, Kijima H.
  • Journal Title: Biomed Res 29 Pages: 251-256
  • NAID: 130004470723
  • Peer Reviewed
• [Journal Article] Claudin-1 expression is induced by tumor necrosis factor-alpha in human pancreatic cancer cells (2008)
  • Author(s): Kondo J, Sato F, Kusumi T, Liu Y, Motonari O, Sato T, Kijima H.
  • Journal Title: Int J Mol Med 22 Pages: 645-649
  • Peer Reviewed
• [Journal Article] Establishment of transplantable murine osteosarcoma cell line with endochondral ossification (2008)
  • Author(s): Nishi T, Kusumi T, Tanaka M, Sato F, Sasaki M, Kudo H, Kijima H
  • Journal Title: Anticancer Res 28 Pages: 1627-1631
  • Peer Reviewed
• [Journal Article] Period is involved in the proliferation of human pancreatic MIA-PaCa2 cancer cells by TNF-α (2008)
  • Author(s): Suzuki T, Sato F, Kondo J, Liu Y, Kusumi T, Fujimoto K, Kato Y, Sato T, Kijima H.
  • Journal Title: Biomed Res 29 Pages: 99-103
  • Peer Reviewed
• [Journal Article] Cardiac tumor comprising two components including typical myxoma and atypical hypercellularity suggesting a malignant change (2008)
  • Author(s): Kusumi T, Minakawa M, Fukui K, Saito S, Ohashi M, Sato F, Fukuda I, Kijima H.
  • Journal Title: Cardiovasc Pathol 10
  • Peer Reviewed
• [Journal Article] Decreased expression of claudin-1 is correlated with recurrence status in esophageal squamous cell carcinoma (2008)
  • Author(s): Miyamoto K, Kusumi T, Sato F, Kawasaki H, Shibata S, Ohashi M, Hakamada K, Sasaki M, Kijima H.
  • Journal Title: Biomed Res 29 Pages: 71-76
  • NAID: 130004724051
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of the carcinoma in the specimen obtained radial prostatectomy following hormone therapy (2008)
  • Author(s): Kusumi T., et.al.
  • Journal Title: Pathol Int 58 Pages: 687-694
  • Peer Reviewed
• [Journal Article] Basic-helix-loop-helix(bHLH)transcription factor DEC2 negatively regulates vascular endothelial growth factore expression (2008)
  • Author(s): Sato, et. al.
  • Journal Title: Genes Cells 13 Pages: 131-144
  • Peer Reviewed
• [Journal Article] Expression of vascular endothelial growth factor by photodynamic therapy with mono-L-aspartyl chlorin e6(NPe6)in oral squamous cell carcinoma (2007)
  • Author(s): Nakagawa H, Matsumiya T, Sakaki H, Imaizumi T, Kubota K, Kusumi A, Kobayashi W, Kimura H.
  • Journal Title: Oral Oncol 43 Pages: 544-550
  • Peer Reviewed
• [Journal Article] Decreased expression of claudin-1 correlates with recurrence status in breast cancer (2007)
  • Author(s): Morohashi S, Kusumi T, Sato F, Odagiri H, Chiba H, Yoshihara S, Hakamada K, Sasaki M, Kijima H
  • Journal Title: Int J Mol Med 20 Pages: 139-143
  • Peer Reviewed
• [Journal Article] Locally administered low-dose alendronate increases bone mineral density during distraction osteogenesis in a rabbit model (2007)
  • Author(s): Omi H, Kusumi T, Kijima H, Toh S
  • Journal Title: J Bone Joint Surg Br. 89 Pages: 984-988
  • Peer Reviewed
• [Journal Article] Expression of vascular endothelial growth factor by photodynamic therapy with mono-L-asparty1 chlorin e6(NPe6)in oral squamous cell carcinoma (2007)
  • Author(s): Nakagawa H, et. al.
  • Journal Title: Oral Oncol 43 Pages: 544-550
  • Peer Reviewed
• [Journal Article] Decreased expression of claudin-1 correlates with recurrence status in breast cancer (2007)
  • Author(s): Morohashi S, et. al.
  • Journal Title: Int J Mol Med 20 Pages: 139-143
  • Peer Reviewed
• [Journal Article] Locally administered low-dose alendronate increases bone mineral density during distraction osteogenesis in a rabbit model (2007)
  • Author(s): Omi H, et. al.
  • Journal Title: J Bone Joint Surg Br 89 Pages: 984-988
  • Peer Reviewed
• [Journal Article] Passage-affected competitive regulation of osteoprotegerin synthesis and the receptor activator of nuclear factor- κ B ligand mRNA expression in normal human osteoblasts stimulated by the application of cyclic tensile strain
  • Author(s): Kusumi A, Kusumi T, Miura J, Tateishi T.
  • Journal Title: J Bone Miner Metabolism (in press)
  • Peer Reviewed
• [Presentation] The influence of culture passages on OPG synthesis and RANKL mRNA expression in normal human osteoblasts stimulated with the application of cyclic tensile strain in itro (2007)
  • Author(s): 楠美昭則
  • Organizer: 第37回日本免疫学会総会学術集会.
  • Place of Presentation: 東京都
  • Year and Date: 2007-11-20
• [Presentation] The influence of culture passages on OPG synthesis and RANKL mRNA expression in normal human osteoblasts stimulated with the application of cyclic tensile strain in vitro (2007)
  • Author(s): 楠美 昭則
  • Organizer: 第37回日本免疫学会総会学術集会
  • Place of Presentation: 東京都
  • Year and Date: 2007-11-20
• [Presentation] 周期的伸展刺激負荷されたヒト骨芽細胞の培養継代回数によるOPG産生とsRANKL発現制御の影響 (2007)
  • Author(s): 楠美昭則、他
  • Organizer: 第61回日本口腔科学会学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2007-04-19
• [Book] Nakane A et al eds. Emerging Theories of Host Defense (2007)
  • Author(s): Kusumi A, Sakaki H, Kusumi T, Nakagawa H, Kubota K, Oda M, Satoh H, Kimura H.
  • Total Pages: 301
  • Publisher: The influence of serial passage on cyclic tensile strain-induced osteoprotegerin synthesis from normal human osteoblasts in vitro. Hirosaki University Press. Hirosaki University Press
• [Book] Emerging Theories of Host Defense (2007)
  • Author(s): Nakane A, et. al. eds
  • Total Pages: 301
  • Publisher: Hirosaki University Press