骨細胞特異的蛋白の血中濃度測定による経済的かつ簡便な骨強度評価法の新規開発

2008 Fiscal Year Annual Research Report

• Project/Area Number: 19390393
• Research Institution: Osaka University
• Principal Investigator: 橋本 淳 Osaka University, 医学系研究科, 准教授 (40237938)
• Co-Investigator(Kenkyū-buntansha): 吉川 秀樹 大阪大学, 医学系研究科, 教授 (60191558) ; 守山 敏樹 大阪大学, 保健センター, 教授 (30283815) ; 名井 陽 大阪大学, 医学部付属病院, 准教授 (10263261) ; 中村 憲正 大阪大学, 医学系研究科, 助教 (50273719)
• Keywords: MEPE / 骨質 / 骨強度 / 骨細胞 / 血漿中濃度 / 酸素分圧 / 動脈硬化 / 健康寿命

Research Abstract

骨細胞特異的蛋白のMEPEの血中濃度測定系を用いて正常値の検討
平成20年度までに血中MEPE濃度測定値の年齢層別、性別の正常値の検討を行うために、健診受診者で承諾の得られた方の血漿サンプル3000件以上を既に得て、血清ALP、無機リン、カルシウム濃度の測定を終えている。このサンプルの中から年齢増別、性別に人数均等になるように合計500人分のサンプルをランダム抽出して、現在MEPEのmonoclonal抗体でのELISAの系で120検体の測定を終え、MEPE monoclonal抗体の系で75%の血漿で感度以下、25%のサンプルで測定可能であった。現在、この感度を改善に関して、測定条件の調整を行っている。骨組織でのMEPEの発現様式:この検討を行う中で骨芽細胞の石灰化に向かう後期分化におけるMEPE, DMP-1, FGF23, Cx43といった骨細胞特異的蛋白の発現は低酸素環境により促進されることを見出した(JBMM25,266,2007)。さらにこの検討結果をふまえ酸素分圧が破骨細胞分化にも関与することを明らかとし(Bone44,71,2009)、また一方動脈硬化血管の中膜の石灰化部の平滑筋細胞でもMEPEの発現が確認され、骨細胞特異的と思われていたMEPEは骨以外の石灰化の場面でも関与していることが明らかとなった。この結果から、現在われわれは骨質を評価する新たな指標としてのMEPEの測定方法の開発は、動脈硬化を含めた石灰化との関与も捕らえ、健康寿命にかかわる骨・血管両者の疾患の病態診断となる可能性を考え上記の血漿中濃度測定の検討を進めている。

Research Products

• [Journal Article] High oxygen tension prolongs the suryival 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 Pages: 71-79
  • Peer Reviewed
• [Journal Article] Serum adiponectin concentrations correlate with severity ofrheumatoid arthritis evaluated by extent of joint des truetion (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 (Epub)
  • Peer Reviewed
• [Journal Article] Adenovirus-mediated gene transfer of adiponectin reduces theseverity of co11agen-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] Treatment of juxta-articular intraosseous cystic lesions inrheumatoid arthritis patients with interconnected porous calcium hydroxyapatite ceramic (2009)
  • Author(s): Kuriyama K, Hashimoto J, Murase T, Fujii M, Nampei A, Hirao M, Tsuboi H, Myoui A, Yoshikawa H
  • Journal Title: Mod Rheumatol (Epub)
  • Peer Reviewed
• [Journal Article] A case report of a patient with refractory adult-onset still's disease who was successfully treated with tocilizumab over6years. (2009)
  • Author(s): Nakahara H, Mima T, Yoshio-Hoshino N, Matsushita M, Hashimoto J, Nishiimoto N
  • Journal Title: Mod Rheumatol (Epub)
  • Peer Reviewed
• [Journal Article] Morphologic analysis of the medullary canal in rheumatoid elbows. (2009)
  • Author(s): Goto A, Murase T, Hashimoto J, Oka K, Yoshikawa H, Sugamoto K.
  • Journal Title: J Shoulder Elbow Surg 18 Pages: 33-37
  • Peer Reviewed
• [Journal Article] Alendronate Treatment Promotes Bone Formation with a Less Anisotropic Microstructure during Intramembranous Ossificationin Rats (2008)
  • Author(s): Kashii M, Hashimoto J, Nakano T, Umakoshi Y, Yoshikawa H
  • Journal Title: J Bone Miner Metab 26 Pages: 24-33
  • Peer Reviewed
• [Journal Article] Characteristics of fracture and related factors in patientswith rheumatoid arthritis (2008)
  • Author(s): Kampei A, Hashimoto J, Koyanagi J, Ono T, Hashimoto H, Tsumaki N, Tomita T, Sugamoto K, Nishimoto N, Ochi T, Yoshikawa H
  • Journal Title: Modern Rheumatology 18 Pages: 180-186
  • Peer Reviewed
• [Journal Article] Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with with vitamin K2 in postmenopausal women (2008)
  • Author(s): Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H
  • Journal Title: J Bone Miner Metab 26 Pages: 260-264
  • Peer Reviewed
• [Journal Article] Radiological study of joint destruetion patterns in rheuma toid flatfoot. (2008)
  • Author(s): Hattori T, Hashimoto J, Tomita T, Kitamura T, Yoshikawa H, Sugamoto K.
  • Journal Title: Clin Rheumatol 27 Pages: 733-737
  • Peer Reviewed
• [Journal Article] Laboratory and febrile features after joint surgery in rheumatoid arthritis patients treated with tocilizumab (2008)
  • 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 (Epub)
  • Peer Reviewed
• [Journal Article] In Vitro Generation of a Scaffold-Free Tissue-Engineered Construct(TEC)Derived from Human Synovia1 Mesenchyma1 stem Ce11s : Biological and Mechanical Properties, and Further Chondrogenic Potential. (2008)
  • Author(s): Ando W, Tateishi K, Katakai D, Hart DA, Higuchi C, Nakata K, Hashimoto J, Fujie H, Shino K, Yoshikawa H. Nakamura N.
  • Journal Title: Tissue Eng Part A 14 Pages: 2041-2049
  • Peer Reviewed
• [Journal Article] Analysis of radiocarpal and midcarpal motion in stable and unstable rheumatoid wrists using3-D computed tomography (2008)
  • Author(s): Arimitsu S, Murase T, Hashimoto J, Oka K, Sugamoto K, Yoshikawa H, Moritomo H.
  • Journal Title: Journal of Hand Surgery 33 Pages: 189-197
  • Peer Reviewed
• [Journal Article] Comparison of human serum with fetal bovine serum for expansion and differentiation of human synovia1 MSC : potential feasibility for clinical app1ications. (2008)
  • Author(s): Tateishi K, Ando W, Higuchi C, Hart DA, Hashimoto J, Nakata K, Yoshikawa H, Nakamura N.
  • Journal Title: Cell Transplant 17 Pages: 549-557
  • Peer Reviewed
• [Presentation] Pinch position is the significant determinant of pinch power in patients with rheumatoid arthritis (2008)
  • Author(s): Akihide Nampei, Jun Hashimoto, Makoto Hirao, Tsuyoshi Murase, Hideki Yoshikawa
  • Organizer: 15^<th> Congress of the Europian Rheumatism and Arthritis Surgical Society(ERASS)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20080606-20080607
• [Presentation] Malleolar lengthening osteotomy for soft tissue balancing inthe correction of varus/valgus deformity during total ankle arthroplasty in patients with rheumatoid arthritis (2008)
  • Author(s): Hirao M, Hashimoto J, Nampei Akihide, Hideki Tsuboi, H. C. Boots, Yoshikawa H
  • Organizer: 15^<th> Congress of the Europian Rheumatism and Arthritis Surgical Society(ERASS)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20080606-20080607
• [Presentation] 高酸素濃度は破骨細胞前駆細胞の持続的供給を促す (2008)
  • Author(s): 山崎直美, 平尾 眞, 南平昭豪, 坪井秀規, 吉川秀樹, 橋本淳
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-29
• [Presentation] 酸素濃度が破骨細胞に与える影響 (2008)
  • Author(s): 山崎直美, 平尾 眞, 南平昭豪, 坪井秀規, 橋本 淳, 吉川秀樹
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-23
• [Presentation] Evaluation of pinch fundion in patients with rheumatoid arthrit is (2008)
  • Author(s): Akihide Nampei, Makoto Hirao, Tsuyoshi Murase, Hideki Yoshikawa, Jun Hashimoto
  • Organizer: 13^<th> International Congress of the Asia Pacific League of Associations for Rheumatism
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2008-09-24
• [Presentation] Nkx3.2 is an important mediator of hypoxia-induced chondrocyte differentiation (2008)
  • Author(s): Kawato Y, Hirao M, Hashimoto J, Tamai N, Yamasaki N, Nampei A, Myoui A, Yoshikawa H
  • Organizer: 30^<th> ASBME annual meeting
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2008-09-12
• [Presentation] Three-Year Extension of the SAMURAI study Confirms Tocilizumab to Prevent Joint Destruction in Patients with Rheumatoif Arthritis (2008)
  • Author(s): Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T. Murata N, D. Van der Heijde
  • Organizer: Annual European Congress of Rheumatology EULAR 2008
  • Place of Presentation: Paris, France
  • Year and Date: 2008-06-11
• [Presentation] Serum Creatine Kinase Activity is Inversely Corretated with Physical Disability, Inflamatory Activity, Rheuamatoid Factor Titer, and Prednisolone Doase in Female Patients with Rheumatoid Arthritis (2008)
  • Author(s): Ebina K, Hashimoto J, Hirao M, Ando W, Nampei A, Yoshikawa H
  • Organizer: Annual European Congress of Rheumatology EULAR 2008
  • Place of Presentation: Paris, France
  • Year and Date: 2008-06-11