Dopamine receptor signaling regulates human osteoclastogenesis.
Project/Area Number |
26860764
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Collagenous pathology/Allergology
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Research Institution | University of Occupational and Environmental Health, Japan |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2016-03-31
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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.
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Report
(3 results)
Research Products
(9 results)
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[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.
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Journal Title
Mod Rheumatol.
Volume: Mar 30
Pages: 1-7
Related Report
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[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.
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Journal Title
Ann Rheum Dis
Volume: in press
Issue: 2
Pages: 389-95
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Mod Rheumatol.
Volume: 24(3)
Issue: 3
Pages: 405-9
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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.
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Journal Title
Mod Rheumatol.
Volume: 24(3)
Issue: 3
Pages: 399-404
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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