Implication of Oxygen Tension in Bone Metabolism

• Project/Area Number: 20591777
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: HASHIMOTO Jun (2010) Osaka University, 医学系研究科, 准教授 (40237938); 南平 昭豪 (2008-2009) Osaka University, 医学系研究科, 助教 (70464245)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Hideki 大阪大学, 医学系研究科, 教授 (60191558) ; MYOUI Akira 大阪大学, 医学部附属病院, 准教授 (10263261) ; SHI Kenrin 大阪大学, 医学系研究科, 助教 (60575893) ; HIRAO Makoto 大阪大学, 医学系研究科, 助教 (10527708) ; 橋本 淳 大阪大学, 医学系研究科, 准教授 (40237938)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 骨・軟骨代謝学 / 低酸素濃度 / 骨形成 / 軟骨分化 / 低酸素 / Nkx3.2 / 転写因子 / 破骨細胞 / 高酸素濃度 / 酸化ストレス / M-CSF / 生存

Research Abstract

We showed that a high oxygen tension markedly prolonged the duration of osteoclast precursor formation in the presence of supporting cells, and also markedly and persistently increased the production of macrophage colony stimulating factor (M-CSF) by supporting cells. These findings could explain some part of pathophysiology in severe bone destruction or osteolysis accompanied with abundant blood vessel and numeraous osteoclasts seen in several pathological conditions such as rheumatoid arthritis (RA) and primary or metastatic tumors. We also showed that O_2 concentrations decreased depending of the depth in both 20 and 5% O_2 tension, so medium depth is one of critical conditions to study the relation of the cellular environment of pericellular oxygen tension and cell biology.

Research Products

• [Journal Article] Humanized anti-interleukin-6 receptor antibody (TOCILIZUMAB) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography and BMI : data from the SAMURAI study. (2011)
  • Author(s): Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N.
  • Journal Title: Mod Rheumatol. 21(1) Pages: 10-5
  • NAID: 10029361106
  • Peer Reviewed
• [Journal Article] TP53 mutations coincide with the ectopic expression of activation-induced cytidine deaminase in the fibroblast-like synoviocytes derived from a fraction of patients with rheumatoid arthritis. (2010)
  • Author(s): Igarashi H, Hashimoto J, Tomita T, Yoshikawa H, Ishihara K.
  • Journal Title: Clin Exp Immunol. 161(1) Pages: 71-80
  • Peer Reviewed
• [Journal Article] Seruadiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction. (2009)
  • Author(s): Ebina K, Fukuhara A, Ando W, Hirao M, Koga T, Oshima T, Matsuda M, Maeda K, Nakamura T, Ochi T, Shimomura I, Yoshikawa H, Hashimoto J.
  • Journal Title: Clinical Rheumatology 28(4) Pages: 445-51
  • Peer Reviewed
• [Journal Article] High oxygen tension prolongs the survival of osteoclast precursors via macrophage colony-stimulating factor Bone. (2009)
  • Author(s): Yamasaki N, Tsuboi H, Hirao M, Nampei A, Yoshikawa H, Hashimoto J.
  • Journal Title: Bone 44(1) Pages: 71-79
  • Peer Reviewed
• [Journal Article] Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice. (2009)
  • Author(s): Ebina K, Oshima K, Matsuda M, Fukuhara A, Maeda K, Kihara S, Hashimoto J, Ochi T, Banda NK, Yoshikawa H, Shimomura I.
  • Journal Title: Biochem Biophys Res Commun. 378 Pages: 186-191
  • Peer Reviewed
• [Journal Article] Laboratory and febrile features after joint surgery in rheumatoid arthritis patients treated with tocilizumab. (2009)
  • Author(s): Hirao M, Hashimoto J, Tsuboi H, Nampei A, Nakahara H, Yoshio N, Mima T, Yoshikawa H, Nishimoto N.
  • Journal Title: Ann Rheum Dis. 68(5) Pages: 654-7
  • Peer Reviewed
• [Journal Article] A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs. (2009)
  • Author(s): Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N.
  • Journal Title: Mod Rheumatol. 19(3) Pages: 273-82
  • NAID: 10025112961
  • Peer Reviewed
• [Journal Article] Specifically modified osteopontin in rheumatoid arthritis fibroblast-like synoviocytes supports interaction with B cells and enhances production of interleukin-6. (2009)
  • Author(s): Take Y, Nakata K, Hashimoto J, Tsuboi H, Nishimoto N, Ochi T, Yoshikawa H.
  • Journal Title: Arthritis Rheum. 60(12) Pages: 3591-601
  • Peer Reviewed
• [Journal Article] High oxygen tension prolongs the survival of osteoclastprecursors via macrophage colony-stimulating factor. (2009)
  • Author(s): Yamasaki N, Tsuboi H, Hirao M, Nampei A, Yoshikawa H, Hashimoto J
  • Journal Title: BONE 44 Pages: 71-79
  • Peer Reviewed
• [Presentation] Pericellular Oxygen Concentration in Osteoblast Culture. (2010)
  • Author(s): H.Oze, Hirao M, Nampei A, Shi K, Yoshikawa H, Hashimoto J.
  • Organizer: 37th European Symposium on Calcified Tissues
  • Year and Date: 2010-06-27
• [Presentation] Adenov irus-mediated Gene Transfer of Adiponectin Reduces Osteoclasts Differentiation and Bone Erosion of Collagen-Induced Arthritis in Mice. (2010)
  • Author(s): K.Ebina, K.Oshima, Hirao M, Hashimoto J, Ochi T, Yoshikawa H, Shimomura I.
  • Organizer: 37th European Symposium on Calcified Tissues
  • Year and Date: 2010-06-27
• [Presentation] Pericellular oxygen concentration in osteoblast culture (2010)
  • Author(s): 小瀬弘樹、橋本淳, 他
  • Organizer: The European Calcified Tissue Society
  • Place of Presentation: Glasgow (UK)
  • Year and Date: 2010-06-26
• [Presentation] Oxidative Stress in Rheumatoid Arthritis (RA) Patients with Tocilizumab Treatment. (2009)
  • Author(s): Hirao M, Yamasaki N, Oze H, Ebina K, Nampei A, Kawato, Y, Yoshikaw H, Nishimoto N, Hashimoto J.
  • Organizer: Annual European Congress of Rheumatoligy 2009
  • Year and Date: 2009-06-10
• [Presentation] Morphological Appearance of Distal Tibia in Patients with Rheumatoid Arthritis. (2009)
  • Author(s): Nampei A, Hirao M, Shi K, Sugamoto K, Yoshikawa H, Hashimoto J.
  • Organizer: Annual European Congress of Rheumatoligy 2009
  • Year and Date: 2009-06-10
• [Presentation] Adenovirus-mediated Gene Transfer of Adiponectin Reduces The Severity of Collagen-induced Arthritis in Mice. (2009)
  • Author(s): Ebina K, Oshima K, Fukuhara A, Matsuda M, Hirao M, Nampei A, Hashimoto J, Yoshikawa H, Shimomura I
  • Organizer: Annual European Congress of Rheumatoligy 2009
  • Year and Date: 2009-06-10
• [Presentation] NKX3.2 is an Important Mediator of Hypoxia-Induced Chodrocytic Differentiation. (2009)
  • Author(s): Kawato Y, Hirao M, Hashimoto J, Tamai T, Yamasaki Y, Nampei A, Myoui A, Yoshikawa H
  • Organizer: 36th European Symposium on Calcified Tissues
  • Year and Date: 2009-05-23