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Dopamine receptor signaling regulates human osteoclastogenesis.

Research Project

Project/Area Number 26860764
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

HANAMI Kentaro  産業医科大学, 医学部, 助教 (50441853)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords神経伝達物質 / 破骨細胞 / ドパミン受容体シグナル / 骨リモデリング
Outline of Final Research Achievements

Human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole reduced the formation of TRAP-positive multi-nucleated cells, cathepsin K mRNA expression, and pit formation area in vitro. These inhibitory effects were reversed by pre-treatment with a D2-like receptor antagonist haloperidol or a Gαi inhibitor pertussis toxin. Dopamine and dopamine D2-like receptor agonists suppressed intracellular cAMP concentration as well as RANKL-meditated induction of c-Fos and NFATc1 mRNA expression in human osteoclast precursor cells. Finally, the dopamine D2-like receptor agonist suppressed LPS-induced osteoclast formation in murine bone marrow culture ex vivo. These findings indicate that dopaminergic signaling plays an important role in bone homeostasis via direct effects upon osteoclast differentiation and further suggest that the clinical use of neuroleptics is likely to affect bone mass.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice.2016

    • Author(s)
      Hirata S, Li W, Kubo S, Fukuyo S, Mizuno Y, Hanami K, Sawamukai N, Yamaoka K, Saito K, Defranoux NA, Tanaka Y.
    • Journal Title

      Mod Rheumatol.

      Volume: Mar 30 Pages: 1-7

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Serum 14-3-3η level is associated with severity and clinical outcomes of rheumatoid arthritis, and its pretreatment level is predictive of DAS28 remission with tocilizumab.2015

    • Author(s)
      Hirata S, Marotta A, Gui Y, Hanami K, Tanaka Y.
    • Journal Title

      Arthritis Res Ther.

      Volume: 17 Issue: 1 Pages: 280-280

    • DOI

      10.1186/s13075-015-0799-7

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching.2015

    • Author(s)
      Kubo S, Nakayamada S, Nakano K, Hirata S, Fukuyo S, Miyagawa I, Hanami K, Saito K, Tanaka Y.
    • Journal Title

      Ann Rheum Dis.

      Volume: Aug 5 Issue: 7 Pages: 207784-207784

    • DOI

      10.1136/annrheumdis-2015-207784

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study.2014

    • Author(s)
      Tanaka Y, Hirata S, Kubo S, Fukuyo S, Hanami K, Sawamukai N, Nakano K, Nakayamada S, Yamaoka K, Sawamura F, Saito K.
    • Journal Title

      Ann Rheum Dis

      Volume: in press Issue: 2 Pages: 389-95

    • DOI

      10.1136/annrheumdis-2013-204016

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Study on the safety and efficacy of tocilizumab, an anti-IL-6 receptor antibody, in patients with rheumatoid arthritis complicated with AA amyloidosis.2014

    • Author(s)
      Miyagawa I, Nakayamada S, Saito K, Hanami K, Nawata M, Sawamukai N, Nakano K, Yamaoka K, Tanaka Y.
    • Journal Title

      Mod Rheumatol.

      Volume: 24(3) Issue: 3 Pages: 405-9

    • DOI

      10.3109/14397595.2013.844294

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effect of interleukin-6 receptor inhibitor, tocilizumab, in preventing joint destruction in patients with rheumatoid arthritis showing inadequate response to TNF inhibitors.2014

    • Author(s)
      Tanaka Y, Takeuchi T, Amano K, Saito K, Hanami K, Nawata M, Fukuyo S, Kameda H, Kaneko Y, Kurasawa T, Nagasawa H, Hoshi D, Sato E, Yamanaka H.
    • Journal Title

      Mod Rheumatol.

      Volume: 24(3) Issue: 3 Pages: 399-404

    • DOI

      10.3109/14397595.2013.843757

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Serum 14-3-3η is a Modifiable, Mechanistic Biomarker that Predicts Tocilizumab Response2015

    • Author(s)
      Kentaro Hanami, Shintaro Hirata, Anthony Marotta, Yoshiya Tanaka
    • Organizer
      欧州リウマチ学会 (第16回)
    • Place of Presentation
      ローマ(イタリア)
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血清14-3-3ηと関節リウマチの疾患活動性の関連についての検討2015

    • Author(s)
      花見健太郎 , 平田信太郎 , 宮川一平 , 久保智史 , 福與俊介 , 澤向範文 , 中野和久 , 中山田真吾 , 齋藤和義 , 田中良哉
    • Organizer
      日本リウマチ学会 (第59回)
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 関節リウマチに対するTocilizumabとAdalimumab投与によるMBDAスコアの12バイオマーカーの挙動比較2015

    • Author(s)
      花見健太郎 , 平田信太郎 , 宮川一平 , 久保智史 , 福與俊介 , 澤向範文 , 中野和久 , 中山田真吾 , 齋藤和義 , 田中良哉
    • Organizer
      日本リウマチ学会 (第59回)
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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