2015 Fiscal Year Final Research Report
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 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | 神経伝達物質 / 破骨細胞 |
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| 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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| Free Research Field |
リウマチ・膠原病
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