Bone and vascular signals during the repair process after bone and bone marrow injury

• Project/Area Number: 18390422
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: SAKAI Akinori University of Occupational and Environmental Health, Japan, 医学部, 准教授 (90248576)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Toshitaka 産業医科大学, 医学部, 教授 (50082235) ; OKIMOTO Nobukazu 産業医科大学, 医学部, 助手 (70330991)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥8,000,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥1,200,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
• Keywords: 骨髄損傷 / 骨芽細胞 / シグナル伝達 / ビタミンA / 血管 / VEGF / PECAM-1 / BMP-2 / HIF / HIF-1 / 骨・骨髄損傷 / HIF-1α / オステオカルシン / 骨形成 / 血管形成 / 髄内仮骨 / flt-1 / 破骨細胞 / 骨吸収 / 代謝回転 / 骨量

Research Abstract

The dis ruption of tyrosine kinase domain of flt-1, one of VEGF (vascular endothelial growth factor) receptors, disturbed osteoblast differentia tion and delayed the repair process after bone and bone marrow injury in mice. The production of alkaline phosphatase increased in osteoblasts co-cultured with endothelial cells. This increase was dose-dependently inhibited by PECAM-1 (platelet endothelial cell adhesion molecule-1) antibody. These findings demonstrated that vascular factors including VEGF and PECAM-1 significantly contributed to osteoblast development in the repairprocess afterbone and bone marrow injury.

Research Products

• [Journal Article] Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill-hole injuries in mice. (2009)
  • Author(s): Katae Y, Tanaka S, Sakai A, Nagashima M, Hirasawa H, Nakamura T
  • Journal Title: Journal of Orthopaedic Research 27巻12号 Pages: 1652-1658
  • Peer Reviewed
• [Journal Article] Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill-hole injuries in mice. (2009)
  • Author(s): Katae Y, Tanaka S, Sakai A, Nagashima M, Hirasawa H, Nakamura T
  • Journal Title: Journal of Orthopaedic Research 27 Pages: 1652-1658
  • Peer Reviewed
• [Journal Article] The anabolic action of intermittent PTH in combination with cathepsin K inhibitor or alendronate differs depending on the remodeling status in bone in ovariectomized mice. (2009)
  • Author(s): Yamane H, Sakai A, Mori T, Tanaka S, Moridera K, Nakamura T
  • Journal Title: Bone 44 Pages: 1055-1062
  • Peer Reviewed
• [Journal Article] 一酸化窒素合成酵素と骨代謝 (2009)
  • Author(s): 佐羽内研、筒井正人、酒井昭典、中村利孝、下川宏明、柳原延章
  • Journal Title: Clinical Calcium 19 Pages: 1133-1141
• [Journal Article] Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells. (2008)
  • Author(s): Menuki K, Mori T, Sakai A, Sakuma M, Okimoto N, Shimizu Y, Kunugita N, Nakamura T
  • Journal Title: Bone 43巻3号 Pages: 613-620
  • Peer Reviewed
• [Journal Article] Genetic disruption of all NO synthase isoforms enhances BMD and bone turnover in mice in vivo: involvement of the renin-angiotensin system. (2008)
  • Author(s): Sabanai K, Tsutsui M, Sakai A, Hirasawa H, Tanaka S, Nakamura E, Tanimoto A, Sasaguri Y, Ito M, Shimokawa H, Nakamura T, Yanagihara N
  • Journal Title: Journal of Bone and Mineral Research 23巻5号 Pages: 633-643
  • Peer Reviewed
• [Journal Article] 骨粗鬆症の予防と治療ガイドライン2006年版に準じた高齢者骨粗鬆症患者の管理 (2008)
  • Author(s): 酒井昭典
  • Journal Title: 老年医学 817-821 Pages: 46-46
  • Peer Reviewed
• [Journal Article] Genetic disruption of all nitric oxide synthase isoforms enhances BMD and bone tournover in mice in vivo : Involvemnet of the renin-angiotension system (2008)
  • Author(s): Sabanai K, Sakai A, Nakamura T, et.al
  • Journal Title: J Bone Miner Res 633-643 Pages: 23-23
  • Peer Reviewed
• [Journal Article] Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissue but not in bone marrow cells. (2008)
  • Author(s): Taketa T, Sakai A, Tanaka S, Nakai K, Menuki K, Yamane H, Tanaka K, Nakamura T
  • Journal Title: J Bone Miner Metab 26 Pages: 143-151
  • NAID: 10024126399
  • Peer Reviewed
• [Journal Article] Genetic disruption of all nitric oxide synthase isoforms enhances BMD and bone turnover in mice in vivo : Involvement of the rennin-angiotensin system. (2008)
  • Author(s): Sabanai K, Tsutsui M, Sakai A, Hirasawa H, Tanaka S, Nakamura E, Tanimoto A, et al.
  • Journal Title: J Bone Miner Res 23 Pages: 633-643
  • Peer Reviewed
• [Journal Article] 骨粗鬆症の予防と治療ガイドライン2006年版に準じた高齢者骨粗鬆症患者の管理 (2008)
  • Author(s): 酒井昭典
  • Journal Title: 老年医学 46 Pages: 817-821
• [Journal Article] Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential. (2007)
  • Author(s): Otomo H, Sakai A, Uchida S, Tanaka S, Watanuki M, Moriwaki S, Niida S, Nakamura T
  • Journal Title: Bone 40巻6号 Pages: 1494-1501
  • Peer Reviewed
• [Journal Article] Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential (2007)
  • Author(s): Otomo H, Sakai A, Nakamura T, et.al
  • Journal Title: Bone 1494-1501 Pages: 40-40
  • Peer Reviewed
• [Journal Article] Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential (2007)
  • Author(s): Otomo H, Sakai A, et. al.
  • Journal Title: Bone 40 Pages: 1494-1501
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 selective inhibitor suppresses restoration of tibial trabecular bone formation in association with restriction of osteoblast maturation in skeletal reloading after hindlimb elevation of mice (2006)
  • Author(s): Nakai K, Sakai A, Nakamura T, et.al
  • Journal Title: Bone 83-92 Pages: 39-39
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 selective inhibition suppresses restoration of tibial trabccular bone formation in association with restriction of osteoblast maturation in skeletal reloading after hindlimb elevation of mice. (2006)
  • Author(s): Nakai K, Nakamura T et al.
  • Journal Title: Bone 39・1 Pages: 83-92
• [Journal Article] Prevalence and involvement pattems of radiographic hand osteoarthritis in Japanese women : the Hizen-Oshima Study. (2006)
  • Author(s): Toba N, Nakamura T et al.
  • Journal Title: J Bone Miner Metab 24・4 Pages: 344-348
• [Presentation] 橈骨遠位端骨折と骨粗鬆症・転倒 (2009)
  • Author(s): 酒井昭典
  • Organizer: 岩国市内科医会学術講演会
  • Place of Presentation: 山口県岩国市(岩国市医療センター医師会病院東館)
  • Year and Date: 2009-04-10
• [Presentation] Skeletal loading enhances osteoblast differentiation and inhibits adipogenic differentiation in bone marrow cells. (2008)
  • Author(s): Sakai A, Menuki K, Nakamura T
  • Organizer: International Society for Fracture Repair, International Symposium on Biophysical Stimulation on Bone and Fracture Healing, Kyoto
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2008-11-26
• [Presentation] Skeletal loading enhances osteoblast differentiation and inhibits adipogenic differentiation in bone marrow cells (2008)
  • Author(s): Sakai A
  • Organizer: International Symposium on Biophysical Stimulation on Bone and Fracture Healing
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2008-11-26
• [Presentation] 一酸化窒素合成酵素完全欠損マウスにおける骨代謝回転の亢進と骨密度の増加 : レニン・アンギオテンシン系の関与 (2008)
  • Author(s): 佐羽内研, 筒井正人, 酒井昭典, 田中伸哉, ほか
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪市(大阪国際会議場)
  • Year and Date: 2008-11-01
• [Presentation] Vitamin A deficiency delays healing process after cortical bone and bone marrowinjury (2007)
  • Author(s): Tanaka K, Sakai A, et. al.
  • Organizer: 29th Annual Mceting of the American Soclety fbr Bone and Mineral Research
  • Place of Presentation: Honolulu,Hawaii,USA
  • Year and Date: 2007-09-19
• [Presentation] Vitamin A deficiency delays healing process after cortical bone and bone marrow injury. (2007)
  • Author(s): Tanaka K, Tanaka S, Sakai A, Hirasawa H, Katae Y, Nakura N, Menuki K, Yamane H, Sabanai K, Shimizu Y, Nakamura T
  • Organizer: The 17th Scientific Meeting International Bone and Mineral Society, Montreal, Canada
  • Place of Presentation: Montreal Convention Centre
  • Year and Date: 2007-06-28
• [Presentation] Vitamin A deficiency delays healing process after cortical bone and bone marrow injury (2007)
  • Author(s): Tanaka K, Sakai A, Nakamura T, et.al
  • Organizer: 17th Scientific Meeting International Bone and Mineral Society
  • Place of Presentation: Montreal, Quebec, Canada
  • Year and Date: 2007-06-28
• [Presentation] Genetic disruption of all nitric oxide synthase isoforms enhances bone tournover and bone mineral density in mice in vivo (2006)
  • Author(s): Sabanai K, Sakai A, Nakamura T, et.al
  • Organizer: 28th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Pennsylvania, Philadelphia, USA
  • Year and Date: 2006-09-15
• [Presentation] Changes of osteoblast development after unloading and reloading in murine models. International symposium (2006)
  • Author(s): Sakai A
  • Organizer: 第24回日本骨代謝学会
  • Place of Presentation: 東京都(東京ファッションタウン)
  • Year and Date: 2006-07-06
• [Presentation] Changes of osteoblast development after unloading and reloading in murine models (2006)
  • Author(s): Sakai A.
  • Organizer: 第24回日本骨代謝学会
  • Place of Presentation: 東京都(東京ファッションタウン)
  • Year and Date: 2006-07-06
• [Book] 1章骨構造と機能細胞とその機能、最新整形外科学大系1運動器の生物学と生体力学(総編集越智隆弘、専門編集中村利孝、吉川秀樹) (2008)
  • Author(s): 酒井昭典
  • Publisher: 中山書店