scholarly journals Two‐day‐treatment of Activin‐A leads to transient change in SV‐HFO osteoblast gene expression and reduction in matrix mineralization

2019 ◽  
Vol 235 (5) ◽  
pp. 4865-4877 ◽  
Author(s):  
Marta Baroncelli ◽  
Ksenija Drabek ◽  
Marco Eijken ◽  
Bram C. J. Eerden ◽  
Jeroen Peppel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Day Treatment ◽  
Activin A ◽  
Matrix Mineralization ◽  
Transient Change

scholarly journals miR-539 mediates osteoblast mineralization by regulating Distal-less genes 2 in MC3T3-E1 cell line

2017 ◽  
Vol 12 (1) ◽  
pp. 294-299 ◽  
Author(s):  
Jianguo Han ◽  
Li Su ◽  
Chunyang Zhang ◽  
Rongcai Jiang
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Cell Line ◽  
Osteoblast Differentiation ◽  
Marker Gene ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
Expression Level ◽  
Matrix Mineralization ◽  
Marker Gene Expression

AbstractmicroRNAs (miRNAs) play an important role in osteoblast differentiation. However, the mechanisms of miRNAs regulating osteoblast mineralization still needs to be further cleared. Distal-less genes 2 (Dlx2) plays an important role in osteoblast differentiation. We have found that miR-539 was significantly downregulated and Dlx2 was found to be inversely correlated with miR-539 in MC3T3-E1 cell line during osteoblast mineralization. The overexpression of miR-539 significantly decreased the expression level of Dlx2 and suppressed the osteogenic marker gene expression level, alkaline phosphatase activity and matrix mineralization. Our study showed that miR-539 was a negative regulator in osteoblast mineralization and that the targeting of Dlx2 gene partly contributes to this inhibitory effect exerted by miR-539.

Myostatin-induced inhibition of the long noncoding RNA Malat1 is associated with decreased myogenesis

2013 ◽  
Vol 304 (10) ◽  
pp. C995-C1001 ◽  
Author(s):  
Rani Watts ◽  
Virginia L. Johnsen ◽  
Jane Shearer ◽  
Dustin S. Hittel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cell Growth ◽  
Noncoding Rna ◽  
Transforming Growth Factor ◽  
Day Treatment ◽  
Global Gene Expression ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Human Skeletal Muscle Cells

Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily of secreted proteins, is a potent negative regulator of myogenesis. Free myostatin induces the phosphorylation of the Smad family of transcription factors, which, in turn, regulates gene expression, via the canonical TGF-β signaling pathway. There is, however, emerging evidence that myostatin can regulate gene expression independent of Smad signaling. As such, we acquired global gene expression data from the gastrocnemius muscle of C57BL/6 mice following a 6-day treatment with recombinant myostatin compared with vehicle-treated animals. Of the many differentially expressed genes, the myostatin-associated decrease (−11.20-fold; P < 0.05) in the noncoding metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was the most significant and the most intriguing because of numerous reports describing its novel role in regulating cell growth. We therefore sought to further characterize the role of Malat1 expression in skeletal muscle myogenesis. RT-PCR-based quantification of C2C12 and primary human skeletal muscle cells revealed a significant and persistent upregulation (4- to 7-fold; P < 0.05) of Malat1 mRNA during the differentiation of myoblasts into myotubes. Conversely, targeted knockdown of Malat1 using siRNA suppressed myoblast proliferation by arresting cell growth in the G0/G1phase. These results reveal Malat1 as novel downstream target of myostatin with a considerable ability to regulate myogenesis. The identification of new targets of myostatin will have important repercussions for regenerative biology through inhibition and/or reversal of muscle atrophy and wasting diseases.

Lenalidomide Up-Regulates SPARC and Inhibits In Vitro Growth of the Malignant Clone in Myelodysplastic Syndrome Patients with 5q Deletion.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 855-855
Author(s):  
Andrea Pellagatti ◽  
Martin Jädersten ◽  
Ann-Mari Forsblom ◽  
Helen Cattan ◽  
Birger Christensson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myelodysplastic Syndrome ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Expression Profiles ◽  
Activin A ◽  
Healthy Controls ◽  
Erythroid Progenitors ◽  
Normal Cells

Abstract The immunomodulatory drug lenalidomide induces cytogenetic remissions in 75% of patients with myelodysplastic syndrome (MDS) and del(5)(q31) through unknown mechanisms. We investigated the in vitro effects of lenalidomide on growth and maturation in differentiating erythroblasts from MDS patients with del(5)(q31) (n=13) and from healthy controls (n=10). Lenalidomide selectively inhibited growth of del(5q) erythroblasts, while not affecting normal cells, including cytogenetically normal cells from MDS del(5q) patients. The inhibitory effect was more pronounced in erythroid than in myeloid cells. In order to gain insight into the mode of action of lenalidomide and to identify the molecular targets of this drug, we have investigated the gene expression profiles of the lenalidomide-treated and untreated intermediate erythroblasts from MDS del(5q) patients (n=9) and from healthy controls (n=8). GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix), covering over 47,000 transcripts representing 39,000 human genes, were used. Treatment with lenalidomide significantly influenced the pattern of gene expression in del(5q) intermediate erythroblasts, with up-regulation of VSIG4, PPIC, TPBG, and SPARC in all samples, and down-regulation of many genes involved in erythropoiesis, including HBA2, GYPA, and KLF1, in most samples. Up-regulation of SPARC (median 4.4-fold, range 2.4–9.5) is of particular interest since SPARC, a gene with known tumor suppressor functions, is both anti-proliferative and anti-angiogenic, and is located at 5q31–q32, within the commonly deleted region in MDS 5q- syndrome. Activin A was one of the most significant differentially expressed genes between lenalidomide-treated cells of MDS del(5q) patients and healthy controls. Activin A is a member of the transforming growth factor-beta superfamily, with pleiotropic functions including apoptosis of hemopoietic cells. We conclude that lenalidomide specifically inhibits growth of del(5q) erythroid progenitors, while not affecting cytogenetically normal cells. These novel findings suggest that up-regulation of SPARC and Activin A may underlie the potent effects of lenalidomide, in particular growth inhibition and anti-angiogenesis, in MDS with del(5)(q31). The localization of the SPARC gene to the CDR of the 5q- syndrome is intriguing and, in relation to the findings of the present study, we suggest that SPARC may well play a role in the molecular pathogenesis of the 5q- syndrome.

Short- and long-term dynamic responses of the metabolic network and gene expression in yeast to a transient change in the nutrient environment

2012 ◽  
Vol 8 (6) ◽  
pp. 1760 ◽  
Author(s):  
Duygu Dikicioglu ◽  
Warwick B. Dunn ◽  
Douglas B. Kell ◽  
Betul Kirdar ◽  
Stephen G. Oliver
Keyword(s):  
Gene Expression ◽  
Metabolic Network ◽  
Dynamic Responses ◽  
Transient Change ◽  
Nutrient Environment ◽  
Short And Long Term

scholarly journals Regulation of globin gene expression in human K562 cells by recombinant activin A

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 765-772 ◽  
Author(s):  
NL Jr Frigon ◽  
L Shao ◽  
AL Young ◽  
L Maderazo ◽  
J Yu
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Chinese Hamster Ovary Cells ◽  
Globin Gene ◽  
Chinese Hamster ◽  
K562 Cells ◽  
Activin A ◽  
Erythroid Cell ◽  
Tgf Beta ◽  
Globin Gene Expression

Recent studies indicate that a purified protein, activin A, belongs to the transforming growth factor beta (TGF-beta) superfamily. Similar to TGF-beta, activin A can have different biologic activities, depending on the target tissues. We used recombinant activin A to demonstrate a possible regulatory role of this protein in modulating human erythroid differentiation in the human erythroid cell line, K562. Using genomic probes containing the second exon of alpha, beta, gamma, and epsilon globins, relative abundance of various types of globin transcripts in untreated and activin-treated K562 cells was examined with S1 nuclease analysis. Despite considerable homology amongst various globin sequences, these globin probes were highly specific for their unique mRNA species in the analyses. It was shown that the abundance of specific globin probe fragments for gamma and epsilon globins (209 nucleotides) as well as alpha (180 nucleotides), which were protected from S1 digestion, increased many fold in K562 cells treated with activin A. In contrast, there were no specific transcripts of beta globin detected in either the control or activin-treated cells. The increases in the level of fetal and embryonic beta-like and alpha globin transcripts also confirmed earlier studies of Northern and slot- blot analyses using globin cDNA as probes. In addition, nuclear run-off transcription assay using isolated nuclei indicated that most of the increase in the globin transcripts after activin treatment could be attributed to the stimulation of transcription rate for globin genes. Transient transfection assays also provide evidence that activin A significantly stimulated transcriptional activity of an epsilon globin promoter in K562, but not in the nonerythroid Chinese hamster ovary cells. Therefore, it was concluded that activin A exerts its effects on globin gene expression at the level of transcription in erythroid cells.

scholarly journals Treatment with valproate downregulates the Agtr2 mRNA in rat lungs

2020 ◽  
Author(s):  
Kadri Seppa ◽  
Anton Terasmaa ◽  
Toomas Jagomäe ◽  
Jürgen Innos ◽  
Eero Vasar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Receptor Agonist ◽  
Animal Studies ◽  
Day Treatment ◽  
The Other ◽  
Gene Expressions ◽  
Rat Lungs ◽  
In Silico Studies ◽  
Agtr2 Gene

AbstractGLP1 receptor agonist liraglutide has been shown to upregulate ACE2 expressions in several animal studies and thereby mediate strong positive stress response1. On the other hand, two in silico studies suggest that valproate downregulates ACE2 and AGTR2 gene expressions2,3. In this study, we have evaluated how these two widely used drugs, liraglutide and valproate, change the expression pattern of RAS system genes in the rat lungs. Our results indicate that eight-day treatment with valproate significantly downregulates the gene expression of Agtr2, Mas1 and Agrt1b in the rat lungs. These effects are reversed by co-administration of liraglutide.

scholarly journals Role of offset and gradient architectures of 3-D melt electrowritten scaffold on differentiation and mineralization of osteoblasts

2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Naghmeh Abbasi ◽  
Saso Ivanovski ◽  
Karan Gulati ◽  
Robert M. Love ◽  
Stephen Hamlet
Keyword(s):  
Gene Expression ◽  
Porous Scaffold ◽  
Osteogenic Potential ◽  
Matrix Mineralization ◽  
Pore Sizes ◽  
Osteogenic Gene Expression ◽  
Scaffold Structure ◽  
Significant Expression ◽  
Matrix Mineralisation

Abstract Background Cell-scaffold based therapies have the potential to offer an efficient osseous regenerative treatment and PCL has been commonly used as a scaffold, however its effectiveness is limited by poor cellular retention properties. This may be improved through a porous scaffold structure with efficient pore arrangement to increase cell entrapment. To facilitate this, melt electrowriting (MEW) has been developed as a technique able to fabricate cell-supporting scaffolds with precise micro pore sizes via predictable fibre deposition. The effect of the scaffold’s architecture on cellular gene expression however has not been fully elucidated. Methods The design and fabrication of three different uniform pore structures (250, 500 and 750 μm), as well as two offset scaffolds with different layout of fibres (30 and 50%) and one complex scaffold with three gradient pore sizes of 250–500 - 750 μm, was performed by using MEW. Calcium phosphate modification was applied to enhance the PCL scaffold hydrophilicity and bone inductivity prior to seeding with osteoblasts which were then maintained in culture for up to 30 days. Over this time, osteoblast cell morphology, matrix mineralisation, osteogenic gene expression and collagen production were assessed. Results The in vitro findings revealed that the gradient scaffold significantly increased alkaline phosphatase activity in the attached osteoblasts while matrix mineralization was higher in the 50% offset scaffolds. The expression of osteocalcin and osteopontin genes were also upregulated compared to other osteogenic genes following 30 days culture, particularly in offset and gradient scaffold structures. Immunostaining showed significant expression of osteocalcin in offset and gradient scaffold structures. Conclusions This study demonstrated that the heterogenous pore sizes in gradient and fibre offset PCL scaffolds prepared using MEW significantly improved the osteogenic potential of osteoblasts and hence may provide superior outcomes in bone regeneration applications.

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