• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analyses on the factors regulating development of ossification of the spinal ligaments

Research Project

Project/Area Number 11671419
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionChiba University

Principal Investigator

YAMAZAKI Masashi  Chiba University, Chiba University Hospital, Assistant professor, 医学部・附属病院, 助手 (50281712)

Co-Investigator(Kenkyū-buntansha) OKAWA Akihiko  Chiba University, Graduate School of Medicine, Assistant professor, 大学院・医学研究科, 助手 (30312945)
MORIYA Hideshige  Chiba University, School of Medicine, Professor, 医学部, 教授 (30092109)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsossification of the spinal ligaments / leptin / leptin receptor / osteogenesis / twy mouse / db / db mouse / polymorphism / Npps (Nucletide phyrophosphatase) / 脊柱靭帯骨化症 / 細胞生物学 / 分子生物学 / 分子遺伝学 / Npps (Nucleotide pyrophosphatase)
Research Abstract

In this study, we analyzed the involvement of Npps and leptin-leptin receptors in development of ossification of the spinal ligaments from the standpoint of biochemistry, cell biology, molecular biology and molecular genetics.
We demonstrated that, in a certain population of OPLL women, serum concentrations of leptin were significantly higher than those in non-OPLL women. In addition, we showed that genes encoding leptin receptor long form and short form were expressed in cultured spinal ligament cells from both OPLL and non-OPLL patients. Administration of leptin and IGF-I in combination increased the proliferation of spinal ligament cells. The results suggest that leptin directly affects the function of spinal ligament cells, and hyperleptinemia seems to be involved in the development of OPLL.
We compared OPLL patients in whom ossification was restricted in cervical spine (Group C) and OPLL patients having ossification not only in cervical spine but also in thoracic and lumbar spines (Group TL). Cervical OPLL frequently occurred in male, whereas thoraco-lumbar OPLL was predominant in female. In female patients, body mass index and serum leptin concentration of Group TL were significantly higher those of Group C.In male patients, incidence of diabetes mellitus was higher in Group TL than in Group C.The results demonstrate that the development of thoraco-lumbar OPLL is strongly related to deviated glucose metabolism in male patients, and obesity and hyperleptinemia in female patients, respectively. Using genomic DNA from OPLL patients, we then analyzed the polymorphism of leptin receptor genes. Between Groups C and TL, however, no significant difference was seen in the polymorphism.
We analyzed twy mice as an animal model for OPLL.In the mice, a missense mutation was identified in the gene coding Npps. Osteopontin was over-expressed in the process of spinal hyperostosis in twy mice. We suggest that osteopontin participates in the onset and progression of human OPLL.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Nakajima F.,: "Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor."J.Orthop.Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kon, T.,: "Expression of osteoprotegerin, RANK-L(osteoprotegerin ligand)and related pro-inflammatory cytokines during fracure healing."J.Bone Miner.Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, H.,: "Spatial and temporal collagen gene expression in the lumbar intertransverse process fusion in rabbits."J.Bone and Joint Surg.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakamura, I.,: "Association of the NPPS gene with ossification of the posterior longitudinal ligament of the spine(OPLL)."Hum Genet. 104. 492-497 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamazaki, M.,: "Spatial and temporal distribution of CD44 and osteopontin in fracture callus."J.Bone and Joint Surg.. 81-B. 508-515 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okawa, A.,: "Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine."Nature Genetics. 19. 271-273 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakajima, F.: "Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor."J.Orthop.Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kon, T.: "Expression of osteoprotegerin, RANK-L (osteoprote gerin ligand) and related pro-inflammatory cytokines during fracture healing."J.Bone Miner.Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, H.: "Spatial and temporal collagen gene expression in the lumbar intertransverse process fusion in rabbits."J.Bone and Joint Surg.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakamura, I.: "Association of the NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL)."Hum Genet. 104. 492-497 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamazaki, M.: "Spatial and temporal distribution of CD44 and osteopontin in fracture callus."J.Bone and Joint Surg.. 81-B. 508-515 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okawa, A.: "Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine."Nature Genetics. 19. 271-273 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 相庭温臣 ほか: "胸腰椎におよぶ後縦靭帯骨化症の特徴"日整会誌. 75(2). 305-305 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 相庭温臣 ほか: "脊椎骨化前駆病変におけるオステオポンチン遺伝子の発現と局在,twyマウスを用いた解析"厚生省特定疾患対策研究事業 脊柱靱帯骨化症に関する調査研究班 平成11年度研究報告書. 13-17 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大河昭彦 ほか: "脊柱靱帯骨化症例におけるレプチン受容体遺伝子多型の解析"厚生省特定疾患対策研究事業 脊柱靱帯骨化症に関する調査研究班 平成11年度研究報告書. 18-20 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中島新 ほか: "レプチン受容体(OB-Rb)欠損マウス・db/dbにおける脊柱靱帯の形態的観察(第2報)"厚生省特定疾患対策研究事業 脊柱靱帯骨化症に関する調査研究班 平成11年度研究報告書. 47-49 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakajima,F., et al: "Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor"J.Orthop.Res.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kon.T., et al: "Expression of osteoprotegerin, RANK-L (osteoprotegerin ligand) and related pro-inflammatory cytokines during fracture healing"J.Bone Miner.Res.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamazaki, M, et al.: "Spatial and temporal distribution of CD44 and osteopontin in fracture callus"J. Bone and Joint Surg. 81-B: 508-515, 1999. 81-B. 508-515 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okawa, A, et al.: "Calcitonin simultaneously regulates both periosteal hyperostosis and trabecular osteopenia in the spinal hyperostotic mouse (twy/twy) in vivo"Calcified Tissue Int 64: 239-247, 1999. 64. 239-247 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 相庭温臣 山崎正志 ほか: "脊柱靭帯骨化症例における血清レプチン濃度およびレプチン受容体遺伝子の発現"日整会誌 73(8):S1761,1999. 73(8). S1761 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中島文毅 山崎正志 ほか: "骨折治癒過程における軟骨形成の分子生物学的解析-塩基性線維芽細胞増殖因子(bFGF)局所投与の効果-"日整会誌 73(8):S1596,1999. 73(8). S1596 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 腰塚裕 大河昭彦 ほか: "後縦靭帯骨化症(OPLL)の遺伝子解析-OPLLモデルマウスttw(tiptoe walking)の原因遺伝子Npps(Nucleotide pyrophosphatase)の単離とOPLL患者におけるNPPS遺伝子多型の解析"日整会誌 73(8):S1758,1999. 73(8). S1758 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okawa, A., et al.: "Mutation in NPPs in a mouse model of ossification of the posterior longitudinal ligament of the spine"Nature Genet. 19: 271-273,1998. 19. 271-273 (1998)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi