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.

scholarly journals In vivo bioluminescence imaging study to monitor ectopic bone formation by luciferase gene marked mesenchymal stem cells

2008 ◽  
Vol 26 (7) ◽  
pp. 901-909 ◽  
Author(s):  
Cristina Olivo ◽  
Jacqueline Alblas ◽  
Vivienne Verweij ◽  
Anton-Jan Van Zonneveld ◽  
Wouter J. A. Dhert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bioluminescence Imaging ◽  
Imaging Study ◽  
Ectopic Bone Formation ◽  
Luciferase Gene ◽  
Ectopic Bone ◽  
In Vivo Bioluminescence Imaging

Alginate Bead-Encapsulated PEDF Induces Ectopic Bone Formation In Vivo in the Absence of Co-Administered Mesenchymal Stem Cells

2018 ◽  
Vol 19 (5) ◽  
pp. 467-478 ◽  
Author(s):  
Mina Elahy ◽  
Michael R. Doschak ◽  
Jeffery D. Hughes ◽  
Swati Baindur-Hudson ◽  
Crispin R. Dass
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Alginate Bead ◽  
Ectopic Bone Formation ◽  
Ectopic Bone

scholarly journals BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of mesenchymal stem cells

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Haozhuo Xiao ◽  
Xiaoyu Wang ◽  
Claire Wang ◽  
Guangming Dai ◽  
Zhenglin Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Blood Vessel ◽  
Osteogenic Differentiation ◽  
Ectopic Bone Formation ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Protein Levels ◽  
Ectopic Bone

Abstract Bone morphogenetic protein (BMP) 9 (BMP9) is one of most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Recently, evidence has shown that osteogenesis and angiogenesis are coupled, however, it is unclear whether BMP9 induces MSC differentiation into endothelial-like cells and further promotes blood vessel formation. In the present study, we explored the potential of BMP9-induced angiogenic differentiation of MSCs, and the relationship between BMP9-induced osteogenic and angiogenic differentiation of MSCs. Osteogenic activities and angiogenic differentiation markers were analyzed at mRNA and protein levels. In vivo osteogenic and angiogenic differentiation of MSCs were tested by the ectopic bone formation model. We identified that adenoviral vectors effectively transduced in immortalized mouse embryonic fibroblasts (iMEFs) and expressed BMP9 with high efficiency. We found that BMP9 induces early and late osteogenic differentiation, and it up-regulated osteogenic marker expression in MSCs. Meanwhile, BMP9 induces angiogenic differentiation of MSCs via the expression of vascular endothelial growth factor a (VEGFa) and CD31 at both mRNA and protein levels. CD31-positive cells were also increased with the stimulation of BMP9. The ectopic bone formation tests found that BMP9-induced trabecular bone formation was coupled with the expression of blood vessel formation markers and sinusoid capillary formation. These findings suggest that BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of MSCs.

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 The Use of Injectable Chitosan/Nanohydroxyapatite/Collagen Composites with Bone Marrow Mesenchymal Stem Cells to Promote Ectopic Bone Formation In Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bo Yu ◽  
Yichen Zhang ◽  
Xiaoming Li ◽  
Qiongren Wang ◽  
Yi Ouyang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Structure ◽  
Ectopic Bone Formation ◽  
Ct Reconstruction ◽  
Bone Mesenchymal Stem Cells ◽  
Inflammatory Reactions ◽  
Ectopic Bone

The aim of this study was to evaluate ectopic in vivo bone formation with or without rat bone mesenchymal stem cells (rBMSCs) of an injectable Chitosan/Nanohydroxyapatite/Collagen (CS/nHAC) composite. The CS/nHAC composites were injected subcutaneously into the backs of Wistar rats with freshly loaded rBMSCs at a density of10×106 cells/mL, and the CS/nHAC composites without cells were used as negative controls. New bone formation, degradation of composites, and degree of calcification were evaluated by Computed Tomography (CT) and three-dimensional (3D) CT reconstruction. Histological evaluations were performed to further assess bone structure and extracellular matrix by HE and Masson staining. The inflammatory reactions related to osteogenesis were also investigated in the present study. In comparison with the CS/nHAC composites, this study revealed that CS/nHAC/rBMSCs composites showed relatively higher percentage of calcification, better establishment of ECM, and less degradation rate. Meanwhile, different extents of inflammatory reactions were also observed in the CS/nHAC and CS/nHAC/rBMSCs explants at 2 and 4 weeks after implantation. Altogether, CS/nHAC/rBMSCs composites are superior to CS/nHAC composites in ectopic bone formation. In conclusion, the rBMSCs-seeded CS/nHAC composites may be beneficial to enhancing ectopic bone formation in vivo.

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