Demonstration of expression of mRNA for particular AMPA and kainate receptor subunits in immature and mature cultured rat calvarial osteoblasts

Hinoi, Eiichi; Fujimori, Sayumi; Takemori, Akihiro; Kurabayashi, Hiroaki; Nakamura, Yoichi; Yoneda, Yukio

doi:10.1016/s0006-8993(02)02726-9

Cited by 46 publications

(34 citation statements)

References 22 publications

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“…In disagreement with the prevailing view that glutamate modulates osteoclastogenesis through NMDA receptors expressed by osteoclasts (25 -27), our present study has clearly demonstrated the complete absence of all glutamatergic machineries from osteoclasts differentiated from bone marrow precursor cells. In our hands, however, functional expression is seen in osteoblasts with glutamatergic signaling machineries, including NMDA (34), AMPA (35), and group III mGluR (36) receptor subtypes for the signal input; EAAT isoforms (37) for the signal termination; and VGLUT1 isoform (38) for the signal output (Fig. 2).…”

Section: Discussionmentioning

confidence: 70%

Pharmacological Topics of Bone Metabolism: Glutamate as a Signal Mediator in Bone

Takarada

Yoneda

2008

J Pharmacol Sci

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Abstract. The view that L-glutamate (Glu) is an excitatory amino acid neurotransmitter in the mammalian central nervous system is prevailing on the basis of successful cloning of a number of genes encoding different signaling molecules, such as Glu receptors for the signal input, Glu transporters for the signal termination and vesicular Glu transporters for the signal output through exocytotic release. Little attention has been paid to an extracellular transmitter role of Glu in peripheral neuronal and non-neuronal tissues, by contrast, whereas recent molecular biological and pharmacological analyses including ours give rise to a novel function for Glu as an autocrine and/ or paracrine signal mediator in bone comprised of osteoblasts, osteoclasts and osteocytes, in addition to other peripheral tissues including pancreas, adrenal and pituitary glands. Emerging evidence suggests that Glu could play a dual role in mechanisms underlying the maintenance of cellular homeostasis as an excitatory neurotransmitter in the central nervous system and as an extracellular signal mediator in peripheral autocrine and / or paracrine tissues. In this review, therefore, we would outline the possible signaling system for Glu to play a role as an extracellular signal mediator in mechanisms underlying maintenance of the cellular homeostasis in bone.

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Section: Discussionmentioning

confidence: 70%

Pharmacological Topics of Bone Metabolism: Glutamate as a Signal Mediator in Bone

Takarada

Yoneda

2008

J Pharmacol Sci

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“…Recent studies have raised the possibility that Glu may be one of the endogenous paracrine (autocrine) factors used for intercellular communications in bone. 25,34 In mammalian osteoblasts constitutive expression is shown with mRNA for non-NMDA receptors such as GluR3 subunit of AMPA receptors as well as KA1 and KA2 subunits of KA receptors, 35 whereas activation of AMPA receptors modulates the exocytotic release of Glu from cultured osteoblasts. 36,37 Moreover, previous studies reveal the functional expression of NMDA receptor channels in osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Glutamate Suppresses Osteoclastogenesis through the Cystine/Glutamate Antiporter

Hinoi

Takarada

Uno

et al. 2007

The American Journal of Pathology

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Previous studies have demonstrated functional expression of different glutamate receptor subtypes (GluRs) in both osteoblasts and osteoclasts. In the present study, we investigated the possible functional expression by osteoclasts of different glutamatergic signaling machineries including GluRs. In disagreement with the aforementioned prevailing view, no mRNA expression was found for all GluRs examined in primary cultured mouse osteoclasts differentiated from bone marrow precursors. Constitutive expression of mRNA was seen with glutamate transporters, such as excitatory amino acid transporters and cystine/glutamate antiporter, in primary osteoclasts. Glutamate significantly inhibited osteoclastogenesis at a concentration over 500 mol/L in both primary osteoclasts and preosteoclastic RAW264.7 cells without affecting the cell viability in a manner sensitive to the antiporter inhibitor. In RAW264.7 cells stably overexpressing the cystine/glutamate antiporter, the inhibition by glutamate was more conspicuous than in cells transfected with empty vector alone. The systemic administration of glutamate significantly prevented the decreased bone mineral density in both femur and tibia in addition to increased osteoclastic indices in ovariectomized mice in vivo. These results suggest that glutamate may play a pivotal role in mechanisms associated with osteoclastogenesis through the cystine/glutamate antiporter functionally expressed by osteoclasts devoid of any GluRs cloned to date. (Am J

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“…In mammalian bone, osteoblasts constitutively express mRNA for non-NMDA receptors such as the GluR3 subunit of AMPA receptors as well as KA1 and KA2 subunits of KA receptors (16), while AMPA receptors modulate the exocytotic release of Glu from cultured osteoblasts (17,18). An antagonist for AMPA receptors was shown to significantly inhibit the release of endogenous Glu in a concentration-dependent manner in MG-63 osteosarcoma cells (17), whereas a paradoxical paper that AMPA facilitates the release of endogenous Glu from cultured osteoblasts in the presence of the inhibitor of AMPA receptor desensitization cyclothiazide is available in the literature (18).…”

Section: Glutamate Signaling In Bonementioning

confidence: 99%

Glutamate Signaling System in Bone

2004

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Abstract. L-Glutamate (Glu) has been thought to be an excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). The hypothesis is supported by successful cloning of a number of genes encoding different signaling molecules, such as Glu receptors for signal input, Glu transporters for signal termination, and vesicular Glu transporters for signal output through exocytotic release. Limited information is available in the literature with regard to an extracellular transmitter role of Glu in peripheral neuronal and non-neuronal tissues, whereas recent molecular biological analyses including ours give rise to a novel function for Glu as an autocrine and / or paracrine factor in bone comprised of osteoblasts, osteoclasts, and osteocytes, in addition to other peripheral tissues including pancreas, adrenal, and pituitary glands. Emerging evidence suggests that Glu could play a dual role in mechanisms underlying maintenance of cellular homeostasis as an excitatory neurotransmitter in the CNS and as an extracellular signal mediator in peripheral autocrine and / or paracrine tissues. In this review, therefore, we summarized the possible signaling by Glu as an extracellular signal mediator in mechanisms underlying maintenance of cellular homeostasis with a focus on bone tissues.

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Demonstration of expression of mRNA for particular AMPA and kainate receptor subunits in immature and mature cultured rat calvarial osteoblasts

Cited by 46 publications

References 22 publications

Pharmacological Topics of Bone Metabolism: Glutamate as a Signal Mediator in Bone

Pharmacological Topics of Bone Metabolism: Glutamate as a Signal Mediator in Bone

Glutamate Suppresses Osteoclastogenesis through the Cystine/Glutamate Antiporter

Glutamate Signaling System in Bone

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