Dopamine D2-like receptor signaling suppresses human osteoclastogenesis

Kentaro Hanami, Kazuhisa Nakano, Kazuyoshi Saito, Yosuke Okada, Kunihiro Yamaoka, Satoshi Kubo, Masahiro Kondo, Yoshiya Tanaka

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of neuroendocrine system to bone metabolism has been emerging, the precise effects of dopaminergic signaling upon osteoclastogenesis remain unknown. Here, we demonstrate that human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole and quinpirole 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, but not with the D1-like receptor antagonist SCH-23390. Dopamine and dopamine D2-like receptor agonists, but not a D1-like receptor agonist, 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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBone
Volume56
Issue number1
DOIs
Publication statusPublished - 2013 Sep
Externally publishedYes

Fingerprint

Dopamine D2 Receptors
Osteoclasts
Osteogenesis
Dopamine
Bone and Bones
Cathepsin K
Quinpirole
Messenger RNA
Neurosecretory Systems
Pertussis Toxin
Dopamine Receptors
Haloperidol
Antipsychotic Agents
Neurotransmitter Agents
Monocytes
Homeostasis
Bone Marrow

Keywords

  • Bone resorption
  • Dopamine receptor
  • Osteoclast

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Hanami, K., Nakano, K., Saito, K., Okada, Y., Yamaoka, K., Kubo, S., ... Tanaka, Y. (2013). Dopamine D2-like receptor signaling suppresses human osteoclastogenesis. Bone, 56(1), 1-8. https://doi.org/10.1016/j.bone.2013.04.019

Dopamine D2-like receptor signaling suppresses human osteoclastogenesis. / Hanami, Kentaro; Nakano, Kazuhisa; Saito, Kazuyoshi; Okada, Yosuke; Yamaoka, Kunihiro; Kubo, Satoshi; Kondo, Masahiro; Tanaka, Yoshiya.

In: Bone, Vol. 56, No. 1, 09.2013, p. 1-8.

Research output: Contribution to journalArticle

Hanami, K, Nakano, K, Saito, K, Okada, Y, Yamaoka, K, Kubo, S, Kondo, M & Tanaka, Y 2013, 'Dopamine D2-like receptor signaling suppresses human osteoclastogenesis', Bone, vol. 56, no. 1, pp. 1-8. https://doi.org/10.1016/j.bone.2013.04.019
Hanami K, Nakano K, Saito K, Okada Y, Yamaoka K, Kubo S et al. Dopamine D2-like receptor signaling suppresses human osteoclastogenesis. Bone. 2013 Sep;56(1):1-8. https://doi.org/10.1016/j.bone.2013.04.019
Hanami, Kentaro ; Nakano, Kazuhisa ; Saito, Kazuyoshi ; Okada, Yosuke ; Yamaoka, Kunihiro ; Kubo, Satoshi ; Kondo, Masahiro ; Tanaka, Yoshiya. / Dopamine D2-like receptor signaling suppresses human osteoclastogenesis. In: Bone. 2013 ; Vol. 56, No. 1. pp. 1-8.
@article{a6681d77313f44a38a8d51b880d4da39,
title = "Dopamine D2-like receptor signaling suppresses human osteoclastogenesis",
abstract = "Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of neuroendocrine system to bone metabolism has been emerging, the precise effects of dopaminergic signaling upon osteoclastogenesis remain unknown. Here, we demonstrate that human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole and quinpirole 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, but not with the D1-like receptor antagonist SCH-23390. Dopamine and dopamine D2-like receptor agonists, but not a D1-like receptor agonist, 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.",
keywords = "Bone resorption, Dopamine receptor, Osteoclast",
author = "Kentaro Hanami and Kazuhisa Nakano and Kazuyoshi Saito and Yosuke Okada and Kunihiro Yamaoka and Satoshi Kubo and Masahiro Kondo and Yoshiya Tanaka",
year = "2013",
month = "9",
doi = "10.1016/j.bone.2013.04.019",
language = "English",
volume = "56",
pages = "1--8",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Dopamine D2-like receptor signaling suppresses human osteoclastogenesis

AU - Hanami, Kentaro

AU - Nakano, Kazuhisa

AU - Saito, Kazuyoshi

AU - Okada, Yosuke

AU - Yamaoka, Kunihiro

AU - Kubo, Satoshi

AU - Kondo, Masahiro

AU - Tanaka, Yoshiya

PY - 2013/9

Y1 - 2013/9

N2 - Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of neuroendocrine system to bone metabolism has been emerging, the precise effects of dopaminergic signaling upon osteoclastogenesis remain unknown. Here, we demonstrate that human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole and quinpirole 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, but not with the D1-like receptor antagonist SCH-23390. Dopamine and dopamine D2-like receptor agonists, but not a D1-like receptor agonist, 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.

AB - Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of neuroendocrine system to bone metabolism has been emerging, the precise effects of dopaminergic signaling upon osteoclastogenesis remain unknown. Here, we demonstrate that human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole and quinpirole 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, but not with the D1-like receptor antagonist SCH-23390. Dopamine and dopamine D2-like receptor agonists, but not a D1-like receptor agonist, 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.

KW - Bone resorption

KW - Dopamine receptor

KW - Osteoclast

UR - http://www.scopus.com/inward/record.url?scp=84878381743&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878381743&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2013.04.019

DO - 10.1016/j.bone.2013.04.019

M3 - Article

C2 - 23631878

AN - SCOPUS:84878381743

VL - 56

SP - 1

EP - 8

JO - Bone

JF - Bone

SN - 8756-3282

IS - 1

ER -