scholarly journals MiR-27a is Essential for the Shift from Osteogenic Differentiation to Adipogenic Differentiation of Mesenchymal Stem Cells in Postmenopausal Osteoporosis

2016 ◽  
Vol 39 (1) ◽  
pp. 253-265 ◽  
Author(s):  
Li You ◽  
Ling Pan ◽  
Lin Chen ◽  
Wensha Gu ◽  
Jinyu Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Postmenopausal Osteoporosis ◽  
Adipogenic Differentiation ◽  
Qrt Pcr ◽  
Msc Differentiation

Background/Aims: Osteoporosis is a progressive bone disease characterized by a decrease in bone mass and density, which results in an increased risk of fractures. Mesenchymal stem cells (MSCs) are progenitor cells that can differentiate into osteoblasts, osteocytes and adipocytes in bone and fat formation. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. MicroRNAs (miRNAs) play a regulatory role in osteogenesis and MSC differentiation. MiR-27a has been reported to be down-regulated in the development of osteoporosis and during adipogenic differentiation. Methods: In this study, a miRNA microarray analysis was used to investigate expression profiles of miRNA in the serum of osteoporotic patients and healthy controls and this data was validated by quantitative real-time PCR (qRT-PCR). MSCs isolated from human and mice with miR-27a inhibition or overexpression were induced to differentiate into osteoblasts or adipocytes. TargetScan and PicTar were used to predict the target gene of miR-27a. The mRNA or protein levels of several specific proteins in MSCs were detected using qRT-PCR or western blot analysis. Ovariectomized mice were used as in vivo model of human postmenopausal osteoporosis for bone mineral density measurement, micro-CT analysis and histomorphometric analysis. Results: Here, we analyzed the role of miR-27a in bone metabolism. Microarray analysis indicated that miR-27a expression was significantly reduced in osteoporotic patients. Analysis on MSCs derived from patients with osteoporosis indicated that osteoblastogenesis was reduced, whereas adipogenesis was increased. MSCs that had undergone osteoblast induction showed a significant increase in miR-27a expression, whereas cells that had undergone adipocyte induction showed a significant decrease in miR-27a expression, indicating that miR-27a was essential for MSC differentiation. We demonstrated that myocyte enhancer factor 2 c (Mef2c), a transcription factor, was the direct target of miR-27a using a dual luciferase assay. An inverse relationship between miR-27a expression and Mef2c expression in osteoporotic patients was shown. Silencing of miR-27a decreased bone formation, confirming the role of miR-27a in bone formation in vivo. Conclusion: In summary, miR-27a was essential for the shift of MSCs from osteogenic differentiation to adipogenic differentiation in osteoporosis by targeting Mef2c.

scholarly journals NEL-Like Molecule-1 (Nell1) Is Regulated by Bone Morphogenetic Protein 9 (BMP9) and Potentiates BMP9-Induced Osteogenic Differentiation at the Expense of Adipogenesis in Mesenchymal Stem Cells

2017 ◽  
Vol 41 (2) ◽  
pp. 484-500 ◽  
Author(s):  
Jing Wang ◽  
Junyi Liao ◽  
Fugui Zhang ◽  
Dongzhe Song ◽  
Minpeng Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Ectopic Bone Formation ◽  
Morphogenetic Protein ◽  
Ectopic Bone ◽  
Bone Morphogenetic Protein 9

Background: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. Methods: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis. In vivo activity was assessed in an ectopic bone formation model of athymic mice. Results: We demonstrate that Nell1 expression was up-regulated by BMP9. Exogenous Nell1 potentiated BMP9-induced late stage osteogenic differentiation while inhibiting the early osteogenic marker. Forced Nell1 expression enhanced BMP9-induced osteogenic regulators/markers and inhibited BMP9-upregulated expression of adipogenic regulators/markers in MSCs. In vivo ectopic bone formation assay showed that exogenous Nell1 expression enhanced mineralization and maturity of BMP9-induced bone formation, while inhibiting BMP9-induced adipogenesis. Conversely, silencing Nell1 expression in BMP9-stimulated MSCs led to forming immature chondroid-like matrix. Conclusion: Our findings indicate that Nell1 can be up-regulated by BMP9, which in turn accelerates and augments BMP9-induced osteogenesis. Exogenous Nell1 may be exploited to enhance BMP9-induced bone formation while overcoming BMP9-induced adipogenesis in regenerative medicine.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

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 Apoptosis Repressor with Caspase Recruitment Domain (ARC) Promotes Bone Regeneration of Bone Marrow-Derived Mesenchymal Stem Cells by Activating Fgf-2/PI3K/Akt Signaling

2021 ◽  
Author(s):  
Longwei Hu ◽  
Yang Wang ◽  
Hongya Pan ◽  
Kathreena Kadir ◽  
Jin Wen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Cell Apoptosis ◽  
New Bone Formation ◽  
Caspase Recruitment Domain

Abstract Objectives: This study aims to investigate whether Apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow -derived mesenchymal stem cells (BMSCs). Materials and methods: The lentivirus transfection method was used to establish ARC -overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC -overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs. Results: ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway. Conclusions: The present study suggests that A RC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

scholarly journals Nanotopography in directing osteogenic differentiation of mesenchymal stem cells: potency and future perspective

2021 ◽  
Author(s):  
Anggraini Barlian ◽  
Katherine Vanya
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Osteogenic Differentiation ◽  
Future Perspective ◽  
Osteogenic Markers

Severe bone injuries can result in disabilities and thus affect a person's quality of life. Mesenchymal stem cells (MSCs) can be an alternative for bone healing by growing them on nanopatterned substrates that provide mechanical signals for differentiation. This review aims to highlight the role of nanopatterns in directing or inducing MSC osteogenic differentiation, especially in bone tissue engineering. Nanopatterns can upregulate the expression of osteogenic markers, which indicates a faster differentiation process. Combined with growth factors, nanopatterns can further upregulate osteogenic markers, but with fewer growth factors needed, thereby reducing the risks and costs involved. Nanopatterns can be applied in scaffolds for tissue engineering for their lasting effects, even in vivo, thus having great potential for future bone treatment.

scholarly journals Apoptosis Repressor with Caspase Domain (ARC) Promotes Bone Regeneration of Bone Marrow Derived Mesenchymal Stem Cells via Activating Fgf-2/PI3K/Akt Signaling

2020 ◽  
Author(s):  
Longwei Hu ◽  
Yang Wang ◽  
Hongya Pan ◽  
Kathreena Kadir ◽  
Jin Wen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Cell Apoptosis ◽  
Pcr Analysis ◽  
New Bone Formation

Abstract Objectives:This study aims to investigate whether ARC could promote survival and enhance osteogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs).Material and methods:Lentivirus transfection method was used to establish ARC overexpressed BMSCs. CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluoresence staining, ALP, ARS assay and RT-PCR analysis. Cells were seeded into CPC scaffolds, then inserted into subcutaneous of nude mice and the defect area of rat’s calvarium. Histological analysis was conducted to evaluate in vivo cell apoptosis and new bone formation ability of ARC overexpressed BMSCs. RNA-seq method was used to detect the possible mechanism of the effect of ARC on BMSCs. Results:ARC can promote BMSCs proliferation and inhibit its cell apoptosis. ARC can enhance BMSCs osteogenic differentiation in vitro. In vivo study revealed ARC can inhibit BMSCs’ apoptosis and increase its new bone formation ability. ARC regulates BMSCs mainly by activating Fgf-2/PI3K/Akt pathway.Conclusions: The present study suggested that ARC is a powerful agent to promote bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

scholarly journals Dentin-derived Inorganic Minerals Promote the Osteogenesis of Bone Marrow-derived Mesenchymal Stem Cells: Potential Applications for Bone Regeneration

2020 ◽  
Author(s):  
Gang Lei ◽  
Yanqiu Wang ◽  
Yan Yu ◽  
Zehan Li ◽  
Jiamin Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Mapk Signaling ◽  
Control Group ◽  
Alizarin Red

Abstract Background Oral and maxillofacial bone loss is highly prevalent among populations and nowadays increased attention has been focused on dentin derivatives as desirable graft materials for bone regeneration. In this study, dentin-derived inorganic minerals (DIM) were fabricated with a high-temperature calcination technique and the effects of DIM on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) and the bone formation were elucidated.Methods The effects of DIM on BMMSCs proliferation, apoptosis capacity were evaluated by CCK-8, flow cytometry and EdU assays. Alkaline phosphatase (ALP) activity detection, ALP staining, alizarin red staining and osteogenic markers expression analysis were performed to investigate the influence of DIM on the osteogenic differentiation of BMMSCs, as well as the relevant signal mechanisms. The model of critical-sized defects in calvarium of rats was constructed for exploring the in vivo efficiency of DIM on bone regeneration.Results Cell viability assays indicated that DIM had no cytotoxicity. BMMSCs cultured with DIM presented a higher level of osteogenic differentiation ability than those in the control group. The activation in ERK and p38 signals was detected in DIM-treated BMMSCs, and both pathways and osteogenic process were suppressed while using ERK inhibitor U0126 and p38 inhibitor SB203580, respectively. Furthermore, the animal experiments revealed that DIM could dramatically enhance new bone formation compared to the control group.Conclusion All these results demonstrated that DIM could promote BMMSCs osteogenic differentiation via triggering ERK and p38 MAPK signaling pathways and be a novel predictable material for facilitating bone formation.

Strontium folic acid derivative functionalized titanium surfaces for enhanced osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo

2017 ◽  
Vol 5 (33) ◽  
pp. 6811-6826 ◽  
Author(s):  
Kui Xu ◽  
Weizhen Chen ◽  
Caiyun Mu ◽  
Yonglin Yu ◽  
Kaiyong Cai
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Folic Acid ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Acid Derivative ◽  
Titanium Surfaces

Strontium folic acid derivative (FASr) functionalized titanium surfaces improve the in vitro osteogenic differentiation of MSCs and osseointegration in vivo.

scholarly journals Dentin-Derived Inorganic Minerals Promote the Osteogenesis of Bone Marrow-Derived Mesenchymal Stem Cells: Potential Applications for Bone Regeneration

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Gang Lei ◽  
Yanqiu Wang ◽  
Yan Yu ◽  
Zehan Li ◽  
Jiamin Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Mapk Signaling ◽  
Control Group ◽  
Alizarin Red

Background. Oral and maxillofacial bone loss is highly prevalent among populations, and nowadays, increased attention has been focused on dentin derivatives serving as desirable graft materials for bone regeneration. In this study, dentin-derived inorganic mineral (DIM) was fabricated with a high-temperature calcination technique and the effects of DIM on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) and the bone formation were elucidated. Methods. The effects of DIM on BMMSC proliferation and apoptosis capacity were evaluated by CCK-8, flow cytometry, and EdU assays. Alkaline phosphatase (ALP) activity detection, ALP staining, alizarin red staining, and osteogenic marker expression analysis were performed to investigate the influence of DIM on the osteogenic differentiation of BMMSCs, as well as the relevant signal mechanisms. The model of critical-sized defects in the calvarium of rats was constructed for exploring the in vivo efficiency of DIM on bone regeneration. Results. Cell viability assays indicated that DIM had no cytotoxicity. BMMSCs cultured with DIM presented a higher level of osteogenic differentiation ability than those in the control group. The activation in ERK and p38 signals was detected in DIM-treated BMMSCs, and both pathways and osteogenic process were suppressed while using ERK inhibitor U0126 and p38 inhibitor SB203580, respectively. Furthermore, the animal experiments revealed that DIM could dramatically enhance new bone formation compared to the control group. Conclusion. DIM could promote BMMSC osteogenic differentiation via triggering the ERK and p38 MAPK signaling pathways and might be a novel predictable material for facilitating bone formation.

scholarly journals Effect of the HDAC inhibitor vorinostat on the osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo

2013 ◽  
Vol 34 (5) ◽  
pp. 699-709 ◽  
Author(s):  
Song Xu ◽  
Kim De Veirman ◽  
Holly Evans ◽  
Gaia Cecilia Santini ◽  
Isabelle Vande Broek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Hdac Inhibitor
Sign in / Sign up

Export Citation Format

Share Document