Nuclear receptor retinoid-related orphan receptor α1 modulates the metabolic activity of human osteoblasts

Benderdour, Mohamed; Fahmi, Hassan; Beaudet, F; Fernandes, Julio C.; Shi, Qin

doi:10.1002/jcb.23141

Cited by 18 publications

(13 citation statements)

References 34 publications

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“…The transcription factors, such as RORA, STAT1, STAT5a, and CEBP, act in regulation of reactive oxygen species production, 19 apoptosis, 20 immunity, 21 and inflammatory response. 22 …”

Section: Resultsmentioning

confidence: 99%

Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome

et al. 2015

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Background The exact mechanisms that underlie the pathological processes of myocardial ischemia in humans are unclear. Cardiopulmonary bypass with cardioplegic arrest allows us to examine the whole transcriptional profile of human left ventricular myocardium at baseline and after exposure to cold cardioplegia induced ischemia as a human ischemia model. Methods We obtained biopsies from 45 patients undergoing aortic valve replacement surgery at baseline and after an average of 79 min of cold cardioplegic arrest. Samples were RNA-sequenced and analyzed with the Partek Genomics Suite for differential expression. Ingenuity Pathway Analysis and Biobase Explain systems were used for functional and pathway analysis. Results Of the 4,098 genes with a mean expression value greater than 5, 90% were downregulated and 9.1% were upregulated. Of those, 1,241 were significantly differentially expressed. Gene ontology analysis revealed significant downregulation in immune inflammatory response and complement activation categories, and highly consistent was the downregulation of intelectin 1, proteoglycan, and SLPI. Upregulated genes of interest were FBJ murine osteosarcoma viral oncogene homolog (FOS) and the hemoglobin genes hemoglobin 1 (HBA1) and hemoglobin beta (HBB). In addition, analysis of transcription factor binding sites revealed interesting targets in factors regulating reactive oxygen species production, apoptosis, immunity, cytokine production, and inflammatory response. Conclusions We have shown that the human left ventricle exhibits significant changes in gene expression in response to cold cardioplegia induced ischemia during cardiopulmonary bypass which provides great insight into the pathophysiology of ventricular ischemia, and thus, may help guide efforts to reduce myocardial damage during surgery.

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“…The transcription factors, such as RORA, STAT1, STAT5a, and CEBP, act in regulation of reactive oxygen species production, 19 apoptosis, 20 immunity, 21 and inflammatory response. 22 …”

Section: Resultsmentioning

confidence: 99%

Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome

et al. 2015

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“…Results of genome-wide association studies (GWAS) or GWAS meta-analyses have demonstrated that RORA is one of the primary risk factors for cardiovascular metabolism ( 29 ). Additionally, RORA serves a role in the regulation of the inflammatory response ( 30 ). In the current study, the expression of RORA was downregulated, which suggested that RORA may be associated with MI.…”

Section: Discussionmentioning

confidence: 99%

Identification of potentially relevant genes for myocardial infarction using RNA sequencing data analysis

Zhao

et al. 2017

Exp Ther Med

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Myocardial infarction (MI) is a heart disease with high morbidity and mortality rates, thus it is critical to identify genes that serve roles during its pathogenesis. The objective of the present study was to identify potentially relevant genes during the progression of the disease. Blood samples from patients with MI and normal controls (n=3/group) were obtained, the RNA was extracted and cDNA libraries were established. RNA sequencing (RNA-seq) was performed on a HiSeq 2500 platform and fragments per kilobase of exon per million fragments mapped was utilized to calculate the gene expression value following preprocessing of the RNA-seq data. Electronic validation of several identified differentially expressed genes (DEGs) was performed on a Gene Expression Omnibus (GEO) dataset GSE59867 (390 cases and 46 healthy controls). Functional enrichment and protein-protein interaction network analysis was conducted for DEGs. A total of 977 DEGs, including 817 upregulated and 160 downregulated genes were identified in patients with MI. These DEGs were significantly enriched for ‘positive regulation of the immune system process,’ ‘inflammatory response,’ ‘regulation of I-kappaB-kinase/NF-kappaB signaling’ and ‘TNF signaling pathway’. A protein-protein interaction network of the top 40 DEGs was used to identify high degree genes, including interferon induced protein with tetratricopeptide repeats 3 (IFIT3), MX dynamin like GTPase 1 (MX1), major histocompatibility complex, class II, DQ α1 (HLA-DQA1), RAR related orphan receptor A (RORA), prostaglandin D2 synthase (PTGDS), cysteine rich protein 2 (CRIP2), collagen type VI α 2 chain (COL6A2) and S100 calcium binding protein P (S100P). The results of validation in the GEO dataset were consistent with the sequencing analysis. A total of eight genes, including IFIT3, MX1, HLA-DQA1, RORA, PTGDS, CRIP2, COL6A2 and S100P may therefore be considered as potentially relevant genes in the pathology of MI.

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“…RORβ has been shown to suppress mineralization and to decrease expression of Bglap (encoding osteocalcin) and Sp7 (encoding osterix) mRNA in cultured murine osteoblasts (52). RORα has been shown to be involved in osteoblast metabolism and RORα-deficient mice have abnormal bone development (53, 54). …”

Section: Retinoid Receptorsmentioning

confidence: 99%

Retinoid Receptors in Bone and Their Role in Bone Remodeling

Henning¹,

Conaway

Lerner

2015

Front. Endocrinol.

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Vitamin A (retinol) is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA), which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RARα, RARβ, RARγ). RARs and closely related retinoid X receptors (RXRα, RXRβ, RXRγ) form heterodimers which bind to DNA and function as ligand-activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver, and processed to ATRA. ATRA’s effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

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Nuclear receptor retinoid-related orphan receptor α1 modulates the metabolic activity of human osteoblasts

Cited by 18 publications

References 34 publications

Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome

Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome

Identification of potentially relevant genes for myocardial infarction using RNA sequencing data analysis

Retinoid Receptors in Bone and Their Role in Bone Remodeling

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