A microarray based identification of osteoporosis-related genes in primary culture of human osteoblasts

Trošt, Zoran; Trebše, Rihard; Preželj, Janez; Komadina, Radko; Logar, Darja Bitenc; Marc, Janja

doi:10.1016/j.bone.2009.09.015

Cited by 66 publications

(58 citation statements)

References 31 publications

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“…In accordance with the present findings, a microarray analysis reveals that xCT mRNA expression is up-regulated in cultured femoral osteoblasts prepared from patients suffering from postmenopausal osteoporosis compared with those from non-osteoporotic patients (37). Although the xCT subunit plays a pivotal role in the biosynthesis of intracellular GSH through promotion of the incorporation of extracellular cystine for intracellular cysteine as a substrate, xCT expression is under the control by the transcription factor nuclear factor erythroid 2-related factor-2 responsible for the regulation of many phase II detoxifying enzymes and oxidative stressinducible proteins in eukaryotic cells exposed to different insults relevant to oxidative stress, including ROS, ionizing radiation, and a variety of chemical entities of electrophile compounds, lipid peroxides, and antioxidants (38 -41).…”

Section: Discussionsupporting

confidence: 92%

A Negative Correlation Between Expression Profiles of Runt-Related Transcription Factor-2 and Cystine/Glutamate Antiporter xCT Subunit in Ovariectomized Mouse Bone

et al. 2011

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Abstract.We have previously demonstrated that glutamate (Glu) suppresses cellular proliferation toward self-renewal through a mechanism associated with the depletion of intracellular GSH after promoting the retrograde operation of the bidirectional cystine/Glu antiporter in undifferentiated osteoblastic MC3T3-E1 cells. In this study, we investigated the expression profile of the xCT subunit of the antiporter as well as the master regulator of osteoblastogenesis runt-related transcription factor-2 (Runx2) in ovariectomized mouse bone. In spinal columns isolated 28 days after ovariectomy, a marked reduction was seen with the intensity of Von Kossa staining used as an index of ossification. In femurs of these ovariectomized mice, a significant decrease was seen in mRNA and protein levels of Runx2 along with increased expression of both mRNA and the corresponding protein for the xCT subunit. To evaluate the possible role of the antiporter in osteoblastogenesis, stable transfectants were established with the xCT subunit toward the culture with osteoblastic differentiation inducers in MC3T3-E1 cells. In stable xCT transfectants cultured under differentiation conditions, marked decreases were seen in nodule formation, Ca 2+ accumulation, and osteoblastic marker gene expression, in addition to downregulation of both mRNA and the corresponding protein for Runx2. Runx2 promoter activity was markedly stimulated in MC3T3-E1 cells transfected with a responsive promoter plasmid after the culture under differentiation conditions, while transient and stable transfection with xCT expression vector invariably prevented the stimulation through an activator protein-1 site. These results suggest that Runx2 expression would be negatively regulated by the cystine/glutamate antiporter expressed by osteoblastic cells at the level of gene transactivation.

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Section: Discussionsupporting

confidence: 92%

A Negative Correlation Between Expression Profiles of Runt-Related Transcription Factor-2 and Cystine/Glutamate Antiporter xCT Subunit in Ovariectomized Mouse Bone

et al. 2011

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“…The microarray data revealed that oxidative stress might be involved in the pathogenesis of osteoporosis. In further in vitro experiments the expression of MT-1G was confirmed to be important in response to oxidative stress in bone cells [86].…”

Section: Osteoporosismentioning

confidence: 86%

“…Genome-wide gene expression was analysed in primary cultures of osteoblasts derived from osteoporotic and non-osteoporotic human bone tissue samples [86]. The microarray data revealed that oxidative stress might be involved in the pathogenesis of osteoporosis.…”

Section: Osteoporosismentioning

confidence: 99%

Microarray analysis of metallothioneins in human diseases—A review

Křížková

Kępińska

Emri

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Microarray analysis of metallothioneins in human diseases AbstractMetallothioneins (MTs), low molecular mass cysteine-rich proteins, which are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions are widely studied due to their functions in detoxification of metals, scavenging free radicals and cells protection against the oxidative stress. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic processes and carcinogenesis. 3The most extensive area is MTs expression for oncological applications, where the information about gene patterns is helpful for the identification biological function, resistance to drugs and creating the correct chemotherapy. In other medical applications the effect of oxidative stress to cell lines exposed to heavy metals and hydrogen peroxide is studied as well as influence of drugs and cytokines on MTs expression and MTs expression in the adiposetissue. The precise detection of low metallothionein concentrations and its isoforms is necessary to understand the connection between quantity and isoforms of MTs to size, localization and type of cancer. This information is necessary for well-timed therapy and increase the chance to survival. Microarray chips appear as good possibility for finding all information about expression of MTs genes and isoforms not only in cancer, but also in other diseases, especially diabetes, obesity, cardiovascular diseases, ageing, osteoporosis, psychiatric disorders and as the effects of toxic drugs and pollutants, which is discussed in this review. List of abbreviations:HCC -hepatocellular carcinoma, HFD -high fat diet, MMP -matrix metalloproteinase, MT -metallothionein, MTF -metal transcription factor, MRE -metal responsive element, ROS -reactive oxygen species.

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“…To address this complex question researchers have also screened differential gene expressions of bone cells using high throughput microarray [14,15]. In most of these studies either the effect of estrogens, corticosteroids oxidative stress or some drugs on osteoblasts have been analyzed [16,17].…”

Section: Introductionmentioning

confidence: 99%

Differential Gene Expression Pattern in Osteoclast Precursor Cells of Indian Postmenopausal Women with and Without Osteoporosis: A Microarray Based Study

Raje¹,

Mhaske²,

Ghosh³

et al. 2017

J Bone Res

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A microarray based identification of osteoporosis-related genes in primary culture of human osteoblasts

Cited by 66 publications

References 31 publications

A Negative Correlation Between Expression Profiles of Runt-Related Transcription Factor-2 and Cystine/Glutamate Antiporter xCT Subunit in Ovariectomized Mouse Bone

A Negative Correlation Between Expression Profiles of Runt-Related Transcription Factor-2 and Cystine/Glutamate Antiporter xCT Subunit in Ovariectomized Mouse Bone

Microarray analysis of metallothioneins in human diseases—A review

Differential Gene Expression Pattern in Osteoclast Precursor Cells of Indian Postmenopausal Women with and Without Osteoporosis: A Microarray Based Study

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