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Analysis of p38 MAP kinase pathway in osteoclasts

Research Project

Project/Area Number 17591955
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YAMASHITA Teruhito  Matsumoto Dental University, Institute for Oral Science, Assistant Professor, 総合歯科医学研究所, 講師 (90302893)

Co-Investigator(Kenkyū-buntansha) UDAGAWA Nobuyuki  Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70245801)
NINOMIYA Tadashi  Matsumoto Dental University, Institute for Oral Science, Research Associate, 総合歯科医学研究所, 助手 (00360222)
NAKAMICHI Yuko  Matsumoto Dental University, Institute for Oral Science, Research Associate, 総合歯科医学研究所, 助手 (20350829)
MIZOGUCHI Toshihide  Matsumoto Dental University, Institute for Oral Science, Assistant Professor, 総合歯科医学研究所, 講師 (90329475)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsosteoclasts / MAP kinase / bone resorption / survival / Yeast Two Hybrid Screening / p38 MAPキナーゼ / MKK6 / アデノウイルスベクター
Research Abstract

Osteoclasts are derived from the monocyte/macrophage lineage and are responsible for bone resorption. p38 MAPK was essential for osteoclast differentiation but the survival and activation of osteoclasts were not affected by SB203580, a specific inhibitor for p38MAPK. Bone resorption factors such as IL-1 and lipopolysaccharide (LPS) activate MAPK signaling. To clarify the role of p38MAPK in osteoclast function, we measured the phosphorylated status of MAPKs and examined whether force-phosphorylation of p38MAPK modulates osteoclast function. Although osteoclasts expressed p38 MAPK at the level equivalent to that of bone marrow macrophages, phosphorylation of p38 MAPK was not induced by LPS in osteoclasts. MKK3 and MKK6, upstream kinases for p38 MAPK, were expressed in osteoclasts. Phosphorylation of MKK3/6 was not increased by IL-1 or LPS, even JNK and ERK were activated. Adenoviral expression of a constitutively active form of MKK6 (MKK6CA) in osteoclasts resulted in phosphorylation of p38 MAPK. The survival activity of MKK6CA-expressing osteoclasts evaluated at 48h was as high as that of IL-1-treated cells. Moreover, the number of survived osteoclasts which expressed MKK6CA decreased to a one third by SB203580. Neither bone resorbing activity on dentin slices nor the expression levels of cathepsin K were different between MKK6CA-expressing osteoclasts and control. These findings suggest that osteoclasts keep own p38 MAPK signaling in an inactive state to abort their survival. In a pathological state, p38 MAPK is activated in osteoclasts and it might extend osteoclast lifespan.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (22 results)

All 2007 2006 2005

All Journal Article (20 results) Book (2 results)

  • [Journal Article] Osteoprotegerin reduces the serum level of receptor activator of NF-KB ligand derived from osteoblasts.2007

    • Author(s)
      Nakamichi Y et al.
    • Journal Title

      J Immunol 178・(1)

      Pages: 192-200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Osteoprotegerin reduces the serum level of receptor activator of NF-kappaB ligand derived from osteoblasts.2007

    • Author(s)
      Nakamichi Y et al.
    • Journal Title

      J Immunology 178(1)

      Pages: 192-200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation following food ingestion.2006

    • Author(s)
      Tsukiyama K et al.
    • Journal Title

      Mol Endocrinol 20・(7)

      Pages: 1644-1651

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation.2006

    • Author(s)
      Itoh S et al.
    • Journal Title

      Bone 39・(3)

      Pages: 502-512

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Osteoblasts provide a suitable microenvironment for the action of receptor activator of NF-κB ligand.2006

    • Author(s)
      Yamamoto Y et al.
    • Journal Title

      Endocrinology 147・(7)

      Pages: 3366-3374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] The mechanism of coupling between bone resorption and bone formation.2006

    • Author(s)
      Udagawa N et al.
    • Journal Title

      J Oral Biosciences 48・(3)

      Pages: 185-197

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin selectively disrupts actin rings without affecting microtubule networks. Submitted for publication.2006

    • Author(s)
      Okumura S et al.
    • Journal Title

      Bone 39・(4)

      Pages: 684-693

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion.2006

    • Author(s)
      Tsukiyama K et al.
    • Journal Title

      Mol Endocrinology 20(7)

      Pages: 1644-1651

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation.2006

    • Author(s)
      Itoh S et al.
    • Journal Title

      Bone 39(3)

      Pages: 505-512

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-kappaB ligand.2006

    • Author(s)
      Yamamoto Y et al.
    • Journal Title

      Endocrinology 147(7)

      Pages: 3366-3374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The mechanism of coupling between bone resorption and bone formation.2006

    • Author(s)
      Udagawa N et al.
    • Journal Title

      J Oral Biosciences 48(3)

      Pages: 185-197

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin disrupts sealing zones without affecting microtubule networks.2006

    • Author(s)
      Okumura S et al.
    • Journal Title

      Bone 39(4)

      Pages: 684-693

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Generation of osteoclasts in vitro, and assay of osteoclast activity.2006

    • Author(s)
      Takahashi N et al.
    • Journal Title

      Arthritis Research, Methods and Protocols, Humana Press Volume 1

      Pages: 285-301

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin selectively disrupts actin ring without affecting microtubule networks. Submitted for publication.2006

    • Author(s)
      Okumura S et al.
    • Journal Title

      Bone 39・(4)

      Pages: 684-693

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dolomite supplementation improves bone metabolism through modulation of calcium-regulating hormone secretion in ovariectomized rats.2005

    • Author(s)
      Mizoguchi T
    • Journal Title

      J Bone Miner Metab 23・2

      Pages: 140-146

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prostaglandin E_2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK1.2005

    • Author(s)
      Kobayashi Y
    • Journal Title

      J Biol Chem 280・12

      Pages: 11395-11403

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prostaglandin E_2 receptors EP2 and EP4 are down-regulated during differentiation of mouse osteoclasts from their precursors.2005

    • Author(s)
      Kobayashi Y
    • Journal Title

      J Biol Chem 280・25

      Pages: 24035-24042

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Muramyl dipeptide enhsnces osteoclast formation induced by lipopolysaccharide, IL-1α and TNF-1α through nucleotide-binding oligomerization domain 2-mediated signaling in osteoblasts.2005

    • Author(s)
      Yang S
    • Journal Title

      J Immunol 175・3

      Pages: 1956-1964

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prostaglandin E_2 strongly inhibits human osteoclasts formation.2005

    • Author(s)
      Take I
    • Journal Title

      Endocrinology 146・12

      Pages: 5204-5214

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nurse-like cells from patients with rheumatoid arthritis support survival of osteoclast precursors via macrophage-colony stimulating factor production.2005

    • Author(s)
      Tsuboi H
    • Journal Title

      Arthritis Rheum 52・12

      Pages: 3819-3828

    • Related Report
      2005 Annual Research Report
  • [Book] Arthritis Research, Methods and Protocols Volume 1 "Generation of osteoclasts in vitro, and assay of osteoclast activity"2006

    • Author(s)
      Takahashi N et al.
    • Publisher
      Humana Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Book] Hard Tissue 硬組織研究ハンドブック2005

    • Author(s)
      松本歯科大学大学院 硬組織研究グループ
    • Total Pages
      261
    • Publisher
      MDU出版会
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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