Functional expression of particular isoforms of excitatory amino acid transporters by rodent cartilage

Hinoi, Eiichi; Wang, Liyang; Takemori, Akihiro; Yoneda, Yukio

doi:10.1016/j.bcp.2005.04.025

Cited by 26 publications

(25 citation statements)

References 27 publications

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“…In mature rat costal chondrocytes, glutamate uptake was demonstrated to occur via the glutamate aspartate transporter and glutamate transporter-1. 30 Moreover, endogenous glutamate was also shown to have an antiproliferative effect. 31 Nevertheless, the influence of glutamate on the production of cartilaginous ECM by mature chondrocytes was not addressed.…”

Section: Discussionmentioning

confidence: 99%

“…It is expected that g-PGA might be consumed/degraded, thus generating a glutamate pool able to activate the glutamate signaling pathway. 96 In fact, glutamate signaling has been described in cartilage, namely in human articular chondrocytes, 28 rat costal and articular chondrocytes, [30][31][32] and also in mouse and human MSCs. [97][98][99] L-glutamate, but not D-glutamate, suppressed mouse MSC proliferation and differentiation in 2D without inducing cell death.…”

Section: Discussionmentioning

confidence: 99%

“…[27][28][29] In cartilage, glutamate signaling was shown to tune rat and human chondrocyte behavior and enhance matrix production. [30][31][32] g-PGA-blended scaffolds were reported to support rat chondrocyte cultures. 33 A patent describing the injection of g-PGA for the treatment of degenerative joint diseases has also been filed.…”

Section: Introductionmentioning

confidence: 99%

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Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells

Antunes

Tsaryk

et al. 2015

Tissue Engineering Part A

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells

Antunes

Tsaryk

et al. 2015

Tissue Engineering Part A

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“…Samples were then separated by SDSpolyacrylamide gel electrophoresis, followed by transfer to nitrocellulose membranes (Millipore) and subsequent immunoblotting assay as described previously (29).…”

Section: Determination Of Alp Activity and Ca 2ϩ Accumulation And Alimentioning

confidence: 99%

Nrf2 Negatively Regulates Osteoblast Differentiation via Interfering with Runx2-dependent Transcriptional Activation

Hinoi

Fujimori

Wang

et al. 2006

Journal of Biological Chemistry

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149

112

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Nrf2 (nuclear factor E2 p45-related factor 2) is believed to be a transcription factor essential for the regulation of many detoxifying and antioxidative genes in different tissues. In the present study, we investigated the role of Nrf2 in the regulation of osteoblastic differentiation. nrf2 mRNA expression was significantly up-regulated in femur isolated from ovariectomized mice, whereas in situ hybridization analysis revealed that up-regulation of nrf2 mRNA was mainly found in osteoblasts attached on cancellous bone in femur of ovariectomized mice. Expression of Nrf2 protein was also seen in osteoblasts in neonatal mouse tibia and calvaria. In osteoblastic MC3T3-E1 cells stably transfected with nrf2 expression vector, significant inhibition was seen in the maturation-dependent increase in alkaline phosphatase activity as well as the mineralized matrix formation. Stable overexpression of nrf2 significantly impaired Runx2 (runt-related transcription factor 2)-dependent stimulation of osteocalcin promoter activity and recruitment of Runx2 on osteocalcin promoter without affecting the expression of runx2 mRNA. Coimmunoprecipitation and mammalian two-hybrid assay revealed a physical interaction between Runx2 and Nrf2, whereas cellular distribution of endogenous Runx2 was not apparently changed by nrf2 overexpression in MC3T3-E1 cells. Alternatively, Nrf2 bound to antioxidant-responsive element-like-2 sequence of osteocalcin promoter. The inhibition by nrf2 on runx2-dependent osteocalcin promoter activity was partially prevented by the introduction of reporter of deletion mutant for ARE-like-2 sequence of osteocalcin promoter. These data suggest that Nrf2 may negatively regulate cellular differentiation through inhibition of the Runx2-dependent transcriptional activity in osteoblasts.In bone tissues, both formation and maintenance are sophisticatedly regulated by bone-forming osteoblasts and bone-resorbing osteoclasts (1-3). The osteoblast lineage is derived from primitive multipotent mesenchymal stem cells with potentiality to differentiate into bone marrow stromal cells, chondrocytes, muscles, and adipocytes (4), whereas osteoclasts are multinucleated cells derived from the fusion of mononuclear hematopoietic precursors (3). The development and differentiation of these two distinct cells are under tight regulation by a number of endogenous substances. These include growth factors, cytokines, and hormones, which are individually secreted through endocrine, paracrine/autocrine, and neurocrine systems essential for the delicate balancing between bone formation and resorption by the two different cells in the bone marrow microenvironment. An imbalance between these two cells leads to pathogenesis and etiology of certain bone metabolic diseases, including osteoporosis and osteopetrosis (5, 6). Ovariectomy has been employed to experimentally establish model animals with bone loss seen in postmenopausal osteoporosis caused by estrogen deficiency (7). In ovariectomized animals, osteoblast indices, such as osteoblast numbe...

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“…The group III mGluR agonist L-(1)-2-amino-4-phosphonobutyrate drastically inhibits chondral mineralization in a manner sensitive to an antagonist in cultured mouse embryonic metatarsals isolated before vascularization (46), while the addition of AMPA markedly evokes the release of endogenous Glu into incubation medium from cultured rat costal chondrocytes with further potentiation by the AMPA receptor desensitization-blocker cyclothiazide (47). Extracellular Glu is taken up into intracellular locations through particular EAAT isoforms functionally expressed by the rodent chondrocytes (48). In addition, Glu could cooperatively regulate cellular differentiation toward mineralization through a mechanism associated with apoptosis after depletion of intracellular GSH due to the possible retrograde operation of the cystine/Glu antiporter, in addition to the activation of group III mGluR, in chondrocytes (49).…”

Section: Cartilagementioning

confidence: 99%

Possible Involvement of Glutamatergic Signaling Machineries in Pathophysiology of Rheumatoid Arthritis

Hinoi

Yoneda

2011

J Pharmacol Sci

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Abstract. The prevailing view is that L-glutamate (Glu) functions as an excitatory amino acid neurotransmitter through a number of molecular machineries required for the neurocrine signaling at synapses in the brain. These include Glu receptors for signal input, Glu transporters for signal termination, and vesicular Glu transporters for signal output through exocytotic release. Although relatively little attention has been paid to the functional expression of these molecules required for glutamatergic signaling in peripheral tissues, recent molecular biological analyses including ours give rise to a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system in several peripheral and non-neuronal tissues, including bone and cartilage. In particular, a drastic increase is demonstrated in the endogenous levels of both Glu and aspartate in the synovial fluid with intimate relevance to increased edema and sensitization to thermal hyperalgesia in experimental arthritis models. However, to date, there is only limited information about the physiological and pathological significance of glutamatergic signaling machineries expressed by articular synovial tissues. In this review, we have outlined the role of Glu in synovial fibroblasts in addition to the possible involvement of glutamatergic signaling machineries in the pathogenesis of joint diseases such as rheumatoid arthritis.

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Functional expression of particular isoforms of excitatory amino acid transporters by rodent cartilage

Cited by 26 publications

References 27 publications

Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells

Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells

Nrf2 Negatively Regulates Osteoblast Differentiation via Interfering with Runx2-dependent Transcriptional Activation

Possible Involvement of Glutamatergic Signaling Machineries in Pathophysiology of Rheumatoid Arthritis

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