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Investigation on the role of osteopontin and CD44 in the osteoclast development

Research Project

Project/Area Number 14571776
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

SUZUKI Keiko  Showa University, Sch Dent., Assistant professor, 歯学部, 講師 (50119187)

Co-Investigator(Kenkyū-buntansha) AMANO Hitoshi  Showa University, Sch Dent., Assistant professor, 歯学部, 講師 (90212571)
SAKAI Nobuhiro  Showa University, Sch Dent., Assistant professor, 歯学部, 助手 (90286849)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsosteoclast / osteopontin / CD44 / Bβ inteerin / bone resorption / OPN- / - mice / bisphosphonate / confocal laser-scannning microscopy / β3 integrin / OPNノックアウトマウス / 骨芽細胞 / CD44 / 細胞骨格
Research Abstract

Osteopontin (OPN) is a highly phosphorylated glycoprotein that is expressed in bone by cells of both the osteoblast and osteoclast lineages. Through an RGD motif, OPN can mediate cell attachment with a preference for the av β3 integrin. Thus, OPN has been shown to have an important role in osteoclastic resorption and to provide a substratum for the attachment of bone lining cells. OPN is also a ligand for CD44, through which it promotes directed cell migration. Since OPN and CD44 are highly expressed in migrating cells, we examined the relationship between these proteins in osteoclasts derived from normal mice and mice with targeted disruption of either the OPN or CD44 genes. Analysis of multinucleated osteoclasts isolated from rat femurs revealed that OPN was primarily localized around the nucleus but was also present in lamellar structures and cell processes which also stained for CD44 and β3 integrin. In non-permeabilized cells, strong surface staining for CD44 and β3, whereas little staining for OPN was observed, reflecting the intracellular location of the OPN and the extracellular location of epitopes for the CD44 and β3. In cells treated with cycloheximide, perinuclear staining for OPN was lost, but iOPN staining was retained within cell processes. Osteoclasts generated from the OPN- or CD44-null mice showed reduced cell spreading, limited protrusion of pseudopodia and impaired cell fusion, resorptive activity compared to wild-type controls. Exogenous OPN could partially restore resorption depth in OPN-null osteoclasts, but not cell mobility or cell fusion indicating that iOPN, co-localizing with CD44 within cell processes and filopodia, is important for the formation and normal function of osteoclasts. These studies indicate that an iOPN co-localizes with CD44 within osteoclast cell processes and filopodia, and that this form of OPN may be important in regulating CD44-mediated cytoskeletal changes associated with osteoclast migration, fusion and resorption.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All 2004 2003 2002 Other

All Journal Article (16 results) Publications (8 results)

  • [Journal Article] Osteopontin colocalizes with CD44 in cell processes in migrating cells and influences the ligation of CD44 by hyaluronan.2004

    • Author(s)
      Suzuki K, Yamada S
    • Journal Title

      Oral Ther Pharmacol 23・3

      Pages: 93-100

    • NAID

      10025694982

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Odontoblasts induced from mesenchymal cells of murine dental papillae in three-dimensional cell culture.2004

    • Author(s)
      Kikuchi H, Suzuki K, Sakai N, Yamada S.
    • Journal Title

      Cell Tissue Res 317・2

      Pages: 173-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin.2004

    • Author(s)
      Zhu B, Suzuki K, Sodek J. et al.
    • Journal Title

      J Cell Physiol 198・1

      Pages: 155-167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteopontin2004

    • Author(s)
      Suzuki K, Sodek J.
    • Journal Title

      日本臨床 62・2

      Pages: 145-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Nuclear Factor of Activated T-cells (NFAT) Rescues Osteoclastogenesis in Precursors Lacking c-Fos.2004

    • Author(s)
      Matsuo K, Galson DL, Zhao C, Peng L, Laplace C, Wang KZQ, Bachler MA, Amano H, Aburatani H, Ishikawa H, Wagner EF
    • Journal Title

      J Biol Chem 279

      Pages: 26475-26780

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteopontin colocalizes with CD44 in cell processes in migrating cells and influences the ligation of CD44 by hyaluronan.2004

    • Author(s)
      Suzuki K, Yamada S
    • Journal Title

      Oral Ther Pharmacol 23(3)

      Pages: 93-100

    • NAID

      10025694982

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteopontin.2004

    • Author(s)
      Suzuki k, Sodek J
    • Journal Title

      Nippon Rinsyo 62(2)

      Pages: 145-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Odontoblasts induced from mesenchymal cells of murine dental papillae in three-dimensional cell culture.2004

    • Author(s)
      Kikuchi H, Suzuki K, Sakai N, Yamada S
    • Journal Title

      Cell & Tissue Res 317(2)

      Pages: 173-185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin.2004

    • Author(s)
      Zhu B, Suzuki K, Goldberg HA, Rittling SR, Denhardt DT, McCulloch CA, Sodek J
    • Journal Title

      J Cell Physiol. 198

      Pages: 155-167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin.2004

    • Author(s)
      Zhu B, Suzuki K, Sodek J.et al.
    • Journal Title

      J Cell Physiol 198・1

      Pages: 155-167

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulatory mechanisms and physiological relevance of a voltage-gated H+ channel in murine osteoclasts : phorbol myristate acetate induces cell acidosis and the channel activation.2003

    • Author(s)
      Mori H, Sakai H, Morihata H, Kawawaki J, Amano H, Yamano T, Kuno
    • Journal Title

      J Bone Miner Res 18

      Pages: 2069-2076

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Regulatory mechanisms and physiological relevance of a voltage-gated H+ channel in murine osteoclasts : phorbol myristate acetate induces cell acidosis and the channel activation.2003

    • Author(s)
      Mori H, Sakai H, Morihata H, Kawawaki J, Amano H, Yamano T, Kuno
    • Journal Title

      J Bone Miner Res. 18

      Pages: 2069-2076

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells.2003

    • Author(s)
      Fujita D, Yamashita N, Iita S, Amano H, Yamada S, Sakamoto K
    • Journal Title

      Prostaglandins Leukot Essent Fatty Acids. 68

      Pages: 351-358

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Colocalization of Intracellular Osteopontin With CD44 is Associated With Migration, Cell Fusion, and Resorption in Osteoclasts.2002

    • Author(s)
      Suzuki K, Zhu B, Sodek J. et al.
    • Journal Title

      J Bone Miner Res 17・8

      Pages: 1486-1497

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Colocalization of intracellular osteopontin with CD44 is associated with migration, cell fusion, and resorption in osteoclasts.2002

    • Author(s)
      Suzuki K, Zhu J, Rittling S, Denhard D.T, Goldberg H.A, McCulloch C.A.G, Sodek J
    • Journal Title

      J Bone Miner Res 17

      Pages: 1486-1497

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Colocalization of Intracellular Osteopontin With CD44 is Associated With Migration, Cell Fusion, and Resorption in Osteoclasts.2002

    • Author(s)
      Suzuki K, Zhu B, Sodek J.et al.
    • Journal Title

      J Bone Miner Res 17・8

      Pages: 1486-1497

    • Related Report
      2004 Annual Research Report
  • [Publications] K.Suzuki, J.Sodek et al.: "Colocalization of Intracellular Osteopontin With CD44 Is Associated With Migration, Cell Fusion, and Resorption in Osteoclasts"J Bone Miner Res.. 17. 1486-1497 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Suzuki, J.Sodek et al.: "Intracellular osteopontin in osteoclasts : Impaired migration, cell fusion and resorption in osteoclasts from OPN-/- and CD44-/- mice"Scientific World J.. 2. 79-81 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Hosoi, T.Yoda, M.Yamaguchi, H.Amano, H.Orimo: "Elderly Women with Oral Exostoses had Higher Bone Mineral Density"J Bone Miner Metab. 21. 120-122 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Suzuki, H.Shinoda et al.: "Evidence for the inhibitory effects of bisphosphonates on osteoclast differentiation and activation obtained using laser scanning confocal microscopy"Bone. 32. S162 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] B.Zhu, K.Suzuki et al.: "Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin"J Cell Physiol.. 198. 155-167 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Suzuki, J.Sodek: "Osteopontin"日本臨床. 62. 145-149 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Suzuki, J.Sodek et al.: "Colocalization of Intracellular Osteopontin With CD44 Is Associated With Migration, Cell Fusion, and Resorption in Osteoclasts"J Bone Miner Res.. Vol.17. 1486-1497 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Hosoi, T.Yoda, M.Yamaguchi, H.Amano, H.Orimo: "Elderly Women with Oral Exostoses had Higher Bone Mineral Density"J Bone Miner Metab. Vol.21. 120-22 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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