P-glycoprotein is expressed in the mineralizing regions of the skeleton

Mangham, D. C.; Cannon, Alexander M.; Komiya, Setsuro; Gendron, Roxanne; Dunussi, K.; Gebhardt, Mark C.; Mankin, Henry J.; Arceci, Robert J.

doi:10.1007/bf02526885

Cited by 16 publications

(9 citation statements)

References 24 publications

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“…Although the function of P-glycoprotein in normal cartilage is not evident from the present study, localization to the hypertrophic region of the growth plate, where marked changes occur in the extracellular environment, suggests an excretory or protective function in normal chondrocytes. The expression of P-glycoprotein in cartilage tumors is consistent with the high level of expression typically observed in other tumors derived from tissue normally expressing this protein [43,44].…”

Section: Discussionsupporting

confidence: 73%

P-glycoprotein expression in cartilaginous tumors

et al. 1997

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Section: Discussionsupporting

confidence: 73%

P-glycoprotein expression in cartilaginous tumors

et al. 1997

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“…The ATP binding cassette (ABC) family of proteins may also transport ATP [5]. In this regard, it has been reported that P-glycoprotein is expressed in the mineralizing regions of the skeleton, suggesting that ABC transporters such as P-glycoprotein may mediate physiological release of ATP in the bone environment [34].…”

Section: Physiological Significance Of Nucleotide-induced Ca 2+ Signamentioning

confidence: 99%

Calcium Signalling via Multiple P2 Purinoceptor Subtypes in Rat Osteoclasts

Wiebe

Sims²,

Dixon³

1999

Cell Physiol Biochem

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Extracellular nucleotides bind to P2 purinoceptors in many tissues. P2X purinoceptors are intrinsic ion channels that mediate depolarization and influx of Ca²⁺, whereas P2Y purinoceptors are coupled through G-proteins to mobilization of intracellular Ca²⁺. Previous studies have yielded conflicting information on the responses of osteoclasts to nucleotides. The purpose of this study was to investigate the pathways underlying purinoceptor-mediated Ca²⁺ signalling in authentic mammalian osteoclasts. Osteoclasts, isolated from the long bones of neonatal rats, were loaded with the Ca²⁺-sensitive probe fura-2 and [Ca²⁺]_i was monitored by microspectrofluorimetry. ATP (10–100 μM) induced transient elevation of [Ca²⁺]_i in 74% of osteoclasts tested. Similar responses were observed in Ca²⁺-free media, consistent with release of Ca²⁺ from intracellular stores. Oscillations in [Ca²⁺]_i were observed only in osteoclasts that had a ‘rounded’ morphology. Responses to selective P2 agonists were consistent with the presence of multiple purinoceptor subtypes, including members of both the P2Y and P2X families. Alendronate, a bisphosphonate with structural similarities to methylene ATP analogues, neither activated nor blocked the Ca²⁺ response mediated by osteoclast purinoceptors. Mechanical stimulation of osteoclasts elicited transient elevation of [Ca²⁺]_i which involved Ca²⁺ influx and, in some cases, release from stores. The nucleotidase apyrase did not inhibit deformation-induced elevation of [Ca²⁺]_i in the presence of extracellular Ca²⁺, indicating that nucleotide release is not essential for mechanically induced Ca²⁺ influx. These findings indicate that osteoclasts exhibit multiple P2 purinoceptor subtypes, linked to elevation of [Ca²⁺]_i.

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“…b MDR expression restricted to growth plate in postnatal cartilage [Mangham et al, 1996;Rosier et al,1997]. c ID2 expressed in hypertrophic cartilage during mouse limb development [Jen et al, 1996].…”

Section: Metabolismmentioning

confidence: 99%

New Chondrocyte Genes Discovered by Representational Difference Analysis of Chondroinduced Human Fibroblasts

Yates¹,

Forbes²,

Glowacki³

2004

Cells Tissues Organs

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This report includes a review of the potential for gene expression analyses to provide new information for solving problems in skeletal repair and regeneration. It focuses on two approaches: high-throughput gene array methods and representational difference analysis (RDA). The principles underlying these methods are presented with experimental tutorials and some applications. Second, this report includes a review of results from applying both approaches to an in vitro model of postnatal chondroinduction by demineralized bone powder (DBP). Human dermal fibroblasts (hDFs) cultured with DBP acquire a chondroblast phenotype and express cartilage-specific matrix proteins after 7 days. We used cDNA macroarrays and RDA to identify the genes that were altered prior to expression of the chondroblast phenotype, i.e., after only 3 days’ culture with DBP. Using a strategy of data management and reduction based upon biological functions, we reported several functional families of genes (cytoskeletal elements, protein synthesis/trafficking, and matrix molecules and their modifiers) that are upregulated during chondroinduction of hDFs. Together with histological and biochemical evidence of the chondroblast phenotype, the gene expression patterns indicate that there are specific stages of induced chondrocyte differentiation in this experimental system. Third, this report includes a new study, in which DBP-regulated genes were used as a data base to derive new information on the cell biology of chondrocytes. The objective was to determine whether a set of genes expressed during induction of chondrocyte differentiation is also expressed by mature articular chondrocytes. Our search of the literature for 59 of the DBP-regulated genes disclosed that expression of 20 of them (33%) had been documented in mature cartilage or chondrocytes. Of the 39 genes not previously documented in cartilage, 11 were tested by RT-PCR and all were found to be expressed in freshly isolated adult human chondrocytes. This review and these new data show how the strategy of high-throughput methods and functional data reduction can expand our knowledge of chondrocyte cell biology.

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P-glycoprotein is expressed in the mineralizing regions of the skeleton

Cited by 16 publications

References 24 publications

P-glycoprotein expression in cartilaginous tumors

P-glycoprotein expression in cartilaginous tumors

Calcium Signalling via Multiple P2 Purinoceptor Subtypes in Rat Osteoclasts

New Chondrocyte Genes Discovered by Representational Difference Analysis of Chondroinduced Human Fibroblasts

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