scholarly journals Novel Regenerative Solutions Induce Rapid Adipogenic Differentiation of Mesenchymal Stem Cells with No Evidence of Transformation or Osteogenic Differentiation

2013 ◽  
pp. 1-15
Author(s):  
Denis Rodgerson ◽  
Alan Harris ◽  
Vincent Giampapa ◽  
Steven Greco ◽  
David O'Neill ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation

scholarly journals Loss of Notch3 Signaling Enhances Osteogenesis of Mesenchymal Stem Cells from Mandibular Torus

2016 ◽  
Vol 96 (3) ◽  
pp. 347-354 ◽  
Author(s):  
X.W. Dou ◽  
W. Park ◽  
S. Lee ◽  
Q.Z. Zhang ◽  
L.R. Carrasco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Underlying Mechanism ◽  
Jaw Bone ◽  
Downstream Target

Mandibular torus (MT) is a common intraoral osseous outgrowth located on the lingual surface of the mandible. Histologic features include hyperplastic bone consisting of mature cortical and trabecular bone. Some theories on the etiology of MT have been postulated, such as genetic factors, masticatory hyperfunction, trauma, and continued growth, but the underlying mechanism remains largely unknown. In this study, we investigated the potential role of mesenchymal stem cells (MSCs) derived from human MT in the pathogenesis of bone outgrowth. We demonstrated that MT harbored a distinct subpopulation of MSCs, with enhanced osteogenic and decreased adipogenic differentiation capacities, as compared with their counterparts from normal jaw bone. The increased osteogenic differentiation of mandibular torus MSCs was associated with the suppression of Notch3 signaling and its downstream target genes, Jag1 and Hey1, and a reciprocal increase in the transcriptional activation of ATF4 and NFATc1 genes. Targeted knockdown of Notch3 expression by transient siRNA transfection promoted the expression of osteogenic transcription factors in normal jaw bone MSCs. Our data suggest that the loss of Notch3 signaling may contribute partly to bone outgrowth in MT, as mediated by enhanced MSC-driven osteogenic differentiation in the jaw bone.

scholarly journals Resveratrol Induces the Osteogenic Differentiation via MiR-320c by Targeting Runx2 and Is Involved in the Adipogenic differentiation of BMSCs

2020 ◽  
Author(s):  
Jilong Zou ◽  
Jianyang Du ◽  
Hualei Tu ◽  
Hongjun Chen ◽  
Kai Cong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Target Gene ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Matrix Mineralization

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are multipotent progenitor cells and have been widely used in clinical therapies due to their multiple pluripotency. Recent publications have found that resveratrol (RSVL) could promote the proliferation and differentiation of mesenchymal stem cells; however, the underlying molecular mechanism of RSVL-induced BMSCs osteogenic differentiation needs to be fully elucidated. The aim of this study was to investigate the function of miRNAs in RSVL-treated BMSCs and its effects on the osteogenic differentiation of BMSCs. Methods BMSCs were cultured and treated with different concentrations of RSVL. After osteogenic differentiation for 20 days, ALP staining was performed to evaluate the ALP activity of BMSCs. And ARS staining was used to detect the matrix mineralization deposition of BMSCs. After adipogenic differentiation for 20 days, adipogenic differentiation was determined by ORO staining for lipid droplets. Quantitative real-time polymerase chain reaction analysis was performed to assess the expression level of target genes. Bioinformatics analysis and luciferase reporter assay was ultilized to examine the relationship between miR-320c and its target gene. Western blot assay was used to analyze the protein expression level of target gene. Results Our results demonstrated that RSVL could promote the osteogenic differentiation and suppressed the adipogenic differentiation of BMSCs in a dose-dependent manner. Besides, a novel regulatory axis containing miR-320c and its target Runx2 was found during the differentiation process of BMSCs under RSVL treatment. Overexpression of miR-320c inhibited the osteogenic differentiation, while knockdown of miR-320c promoted the osteogenic differentiation of BMSCs. In contrast, overexpression of miR-320c accelerated the adipogenic differentiation, while knockdown of miR-320c restrained the adipogenic differentiation of BMSCs. Our results confirm that Runx2 was the directly target of miR-320c in RSVL-promoted osteogenic differentiation of BMSCs. Conclusions The present study revealed that miR-320c might possess the potentials as a novel clinical target for medical intervention to regulate the biological functions of RSVL in BMSCs.

314 ADIPOSE- AND BONE MARROW-DERIVED MESENCHYMAL STEM CELLS PRESENT LARGE SIMILARITIES IN TRANSCRIPTOME PRIOR TO AND DURING ADIPOGENIC AND OSTEOGENIC DIFFERENTIATION

2011 ◽  
Vol 23 (1) ◽  
pp. 253 ◽  
Author(s):  
E. Monaco ◽  
M. Bionaz ◽  
A. Lima ◽  
W. L. Hurley ◽  
M. B. Wheeler
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Antigen Presentation ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Cell Types ◽  
Significant Enrichment ◽  
Post Hoc

Previous data support adipose-derived stem cells as an alternative to bone marrow as a source of adult stem cells for therapeutic purposes. The aim of the present study was to directly compare the transcriptome of adipose-derived (ADSC) and bone marrow-derived (BMSC) mesenchymal stem cells prior to differentiation and during in vitro osteogenic and adipogenic differentiation. The ADSC and BMSC were harvested from 3 adult pigs and differentiated in vitro into adipocytes and osteocytes for up to 4 weeks. Prior to differentiation and at differentiation day 2, 7, and 21, cells were harvested and RNA extracted for transcriptomics analysis by a 13 263 oligo 70-mers array (Sus scrofa AROS V1.0 with extension; Operon). Data were normalized by Lowess and statistical analysis was run using ANOVA with Benjamini-Hochberg false discovery rate (FDR) correction. Data mining was carried out using Ingenuity Pathway Analysis and David. Using an FDR of <0.05 for overall tissue effect and a post-hoc correction of P < 0.001, we observed 65 differentially expressed genes (DEG) between ADSC and BMSC before starting differentiation (0.66% of unique genes in the array). Functional analysis uncovered significant enrichment of extracellular matrix genes with direct roles in cell adhesion, migration, movement, and morphology. When the interaction cell type × differentiation × time was assessed, we observed >2 000 DEG with an FDR <0.05. This large number was mostly due to time effects. When pair-wise comparisons between cell types for each time point during the same differentiation were performed (post-hoc P < 0.001), we observed a strikingly low number of DEG. The number of DEG was lower between cell types in osteogenic (<100 DEG) compared with adipogenic (<200 DEG) differentiation. We observed significant enrichment (FDR-corrected P-value cut-off <0.05) of functions related to metabolism, antigen presentation, angiogenesis, and cell cycle in both differentiation conditions. We also observed an overall greater induction of the enriched functions in ADSC and a decrease in BMSC during adipogenic differentiation and the opposite during osteogenic differentiation except for metabolism, which appeared to be larger in ADSC in all cases. Among the significant enriched functions of DEG between the 2 differentiations, we observed enrichment of genes involved in metabolism, cell death, cell-to-cell signalling, and antigen presentation in ADSC during adipogenic compared with osteogenic differentiation. In BMSC we observed enrichment of functions related to cell death, antigen presentation, and lipid metabolism in osteogenic v. adipogenic differentiation. Overall data uncovered a high similarity at the transcriptional level between ADSC and BMSC both prior to differentiation and during differentiation. Those data support ADSC being particularly similar to BMSC. This work was support by the Illinois Regenerative Medicine Institute (IDPH # 63080017).

Mycophenolic Acid Inhibits the Proliferation and Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Guanosine Depletion.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1454-1454 ◽  
Author(s):  
Weijie Cao ◽  
Lizhen Liu ◽  
Xiaoyu Lai ◽  
Xiaohong Yu ◽  
He Huang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Dependent Manner ◽  
Oil Red O Staining ◽  
Oil Red O

Abstract Abstract 1454 Poster Board I-477 Introduction Mycophenolate mofetil is now widely used in transplantation as a potent immunosuppressant, whose active metabolite is mycophenolic acid (MPA). MPA inhibits de novo purine biosynthesis by reversible, noncompetitive inhibition of inosine monophosphate dehydrogenase (IMPDH). The inhibition of IMPDH in lymphocytes reduces intracellular guanine nucleotide pools, thus arrests lymphocytes proliferation. Recently investigators reported the antiproliferative effects of MPA on fibroblasts, smooth muscle cells and endothelial cells, but there is no reports of the effects of MPA on human bone marrow-derived mesenchymal stem cells (MSCs). Here we examined the effects of MPA on the proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Methods Bone marrow aspirates were obtained from healthy volunteers after informed consent, and MSCs were expanded from bone marrow mononuclear cells by discarding non-adherent cells. For proliferation and survival assays, MSCs were treated with MPA at the concentration of 1μM, 10μM, 50μM, and 100μM. Cell proliferation was analyzed using CCK-8 method (Dojindo). Cell viability was assessed by trypan blue exclusion. Apoptosis was detected by PI/Annexin V assay kit (Invitrogen). To assess the effects of MPA on MSCs differentiation, osteogenic differentiation and adipogenic differentiation were induced in the presence of MPA. For the detection of osteogenic differentiation, the deposited minerals was stained with silver by the method of von Kossa and Ca2+ contents was quantified with calcium colorimetric assay kit (Biovision). Adipogenic differentiation was analyzed by Oil Red O staining and Oil Red O staining extraction. Results In the range of 1μM to 100μM, MPA caused a significant subdued proliferation rate of MSCs in a concentration- and time-dependent manner. After 7d of incubation with MPA at the concentration of 1μM, 10μM, 50μM, and 100μM, the proliferation rate was reduced to 65.33±11.03%, 24±3.74%, 15.33±4.03%, and 15.33±6.94% respectively (P<0.01). Adding guanosine (100μM) to the culture restored the proliferation rate (P<0.01) indicating that MPA exerted antiproliferative effects by guanosine depletion. Trypan blue staining showed that there was no statistically significant difference in the ratio of living cells between MPA treated cells and the control group (P>0.05), and PI/Annexin V staining showed no apoptosis induce by MPA. Von Kossa stainnging indicated that treatment with MPA reduced Ca2+ deposition during osteogenic differentiation of MSCs, and Ca2+ quantification further confirmed that MPA inhibited osteogenic differentiation in a concentration-dependent manner. Ca2+ quantification was 78.43±12.79 μg/well and 22.8±6.58 μg/well respectively at the concentration of 10μM and 100μM of MPA, which were significantly lower than the control group(118.33±12.50ug/well, P<0.05). Oil Red O staining and Quantification of lipid contents showed that MPA had no effect on lipid production during adipogenic differentiation. Conclusion Our study demonstrated that MPA inhibited the proliferation of MSCs by guanosine depletion, and also inhibited the osteogenic differentiation in a concentration-dependent manner. However, MPA had no impact on adipogenic differentiation in vitro. Disclosures No relevant conflicts of interest to declare.

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