Dopamine D2-like receptor signaling suppresses human osteoclastogenesis

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

doi:10.1016/j.bone.2013.04.019

Cited by 50 publications

(50 citation statements)

References 45 publications

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“…5). Consistent with previous work, dopamine suppressed osteoclast differentiation [28]. Risperidone alone did not have any significant impact on osteoclast numbers in these experiments, however, in the presence of dopamine, RIS antagonized the dopamine-induced suppression of osteoclast differentiation (Fig.…”

Section: Resultssupporting

confidence: 91%

“…Dopamine is present in bone marrow; however, data demonstrating a role for local dopamine signaling in the regulation of bone turnover are sparse. Consistent with our findings, dopamine and a D2R agonist have been shown to suppress osteoclast differentiation in human CD14+ cells isolated from peripheral blood mononuclear cells [28]. In vivo, mice with a deletion of the dopamine transporter gene ( DAT − / − mice), which is responsible for dopamine reuptake into presynaptic terminals, have low trabecular bone mass [32].…”

Section: Discussionsupporting

confidence: 79%

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A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice

Motyl

Beauchemin

Barlow

et al. 2017

Bone

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Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8 weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs.

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 79%

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice

Motyl

Beauchemin

Barlow

et al. 2017

Bone

View full text Add to dashboard Cite

show abstract

“…Robust expression of protein and mRNA for D1R, D2R, D3R and D4R was also shown in elderly human microglia, while expression of D5R is less clear (Mastroeni et al, 2009). Other studies have also confirmed the expression of dopamine receptors on human monocytes, macrophages and monocyte-derived osteoclasts (McKenna et al, 2002; Liang et al, 2008; Hanami et al, 2013)…”

Section: Dopamine Regulation Of the Peripheral Immune Systemmentioning

confidence: 65%

The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease

Mackie

Lebowitz

Saadatpour

et al. 2018

Brain, Behavior, and Immunity

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The second-most common neurodegenerative disease, Parkinson's Disease (PD) has three hallmarks: dysfunctional dopamine transmission due, at least in part, to dopamine neuron degeneration; intracellular inclusions of α-synuclein aggregates; and neuroinflammation. The origin and interplay of these features remains a puzzle, as does the underlying mechanism of PD pathogenesis and progression. When viewed in the context of neuroimmunology, dopamine also plays a role in regulating peripheral immune cells. Intriguingly, plasma dopamine levels are altered in PD, suggesting collateral dysregulation of peripheral dopamine transmission. The dopamine transporter (DAT), the main regulator of dopaminergic tone in the CNS, is known to exist in lymphocytes and monocytes/macrophages, but little is known about peripheral DAT biology or how DAT regulates the dopaminergic tone, much less how peripheral DAT alters immune function. Our review is guided by the hypothesis that dysfunctional peripheral dopamine signaling might be linked to the dysfunctional immune responses in PD and thereby suggests a potential bidirectional communication between central and peripheral dopamine systems. This review seeks to foster new perspectives concerning PD pathogenesis and progression.

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“…One influence of immune signals can be to trigger disequilibrium of bone remodeling by affecting the differentiation of osteoclasts or the secretion of pro-inflammatory cytokines. Additionally, accumulating evidence indicates an intriguing role for the dopaminergic system in fine-tuning immune responses [17] and exerting direct effects on bone resorption [18]. Therefore, the fields of neuroimmunology and osteoimmunology are tightly integrated.…”

Section: Discussionmentioning

confidence: 99%

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis

Wei

Sun

Kong

et al. 2016

BMC Musculoskelet Disord

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BackgroundDopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA.MethodsPatients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence.ResultsThere were more DR2+CD19+ B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05).ConclusionThe frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2+CD19+ B cells in synovial tissues might have a role in bone metabolism and TNF-α production.

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Dopamine D2-like receptor signaling suppresses human osteoclastogenesis

Cited by 50 publications

References 45 publications

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice

The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis

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