scholarly journals MicroRNA-378 Promotes Osteogenesis-Angiogenesis Coupling in BMMSCs for Potential Bone Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Bo Zhang ◽  
Yali Li ◽  
Yang Yu ◽  
Jinlong Zhao ◽  
Yangzhen Ou ◽  
...  

Bone tissue regeneration was closely associated with osteogenesis and angiogenesis. The harmonious regulation of osteogenetic and angiogenic growth factors would enhance bone regeneration, while the imbalance of that would lead to local excessive bone formation or vascular mass due to exogenous delivery. Therefore, microRNA is believed to regulate multiple metabolism progress through endogenous signaling pathways on the gene level. In this work, we identified microRNA 378 as a positive regulator of osteogenesis and angiogenesis simultaneously and also observed an increase of microRNA 378 than control in human bone marrow mesenchymal stem cells (hBMMSCs) after osteoblast induction. Besides, osteogenetic and angiogenic gene expression increased simultaneously after overexpression of microRNA 378. Moreover, alizarin red staining and alkaline phosphatase (ALP) staining enhanced, and secretion of vascular endothelial growth factor (VEGF) increased. In this way, we believed miR378 was an ideal target to osteogenesis-angiogenesis coupling for bone regeneration, which provides a potential tool for the gene therapy of bone regeneration.

2018 ◽  
Vol 9 ◽  
pp. 204173141880863 ◽  
Author(s):  
Qiang Chang ◽  
Junrong Cai ◽  
Ying Wang ◽  
Ruijia Yang ◽  
Malcolm Xing ◽  
...  

Soft tissue generation, especially in large tissue, is a major challenge in reconstructive surgery to treat congenital deformities, posttraumatic repair, and cancer rehabilitation. The concern is along with the donor site morbidity, donor tissue shortage, and flap necrosis. Here, we report a dissection-free adipose tissue chamber–based novel guided adipose tissue regeneration strategy in a bioreactor of elastic gelatin cryogel and polydopamine-assisted platelet immobilization intended to improve angiogenesis and generate large adipose tissue in situ. In order to have matched tissue mechanics, we used 5% gelatin cryogel as growth substrate of bioreactor. Platelets from the platelet-rich plasma were then immobilized onto the gelatin cryogel with the aid of polydopamine to form a biomimetic bioreactor (polydopamine/gelatin cryogel/platelet). Platelets on the substrate led to a sustained high release in both platelet-derived growth factor and vascular endothelial growth factor compared with non-polydopamine-assisted group. The formed bioreactor was then transferred to a tissue engineering chamber and then inserted above inguinal fat pad of rats without flap dissection. This integrate strategy significantly boomed the vessel density, stimulated cellular proliferation, and upregulated macrophage infiltration. There was a noticeable rise in the expression of dual-angiogenic growth factors (platelet-derived growth factor and vascular endothelial growth factor) in chamber fluid; host cell migration and host fibrous protein secretion coordinated with gelatin cryogel degradation. The regenerated adipose tissue volume gained threefold larger than control group (p < 0.05) with less fibrosis tissue. These results indicate that a big well-vascularized three-dimensional mature adipose tissue can be regenerated using elastic gel, polydopamine, platelets, and small fat tissue.


Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 497 ◽  
Author(s):  
Moumita Ghosh ◽  
Michal Halperin-Sternfeld ◽  
Itzhak Grinberg ◽  
Lihi Adler-Abramovich

The high demand for tissue engineering scaffolds capable of inducing bone regeneration using minimally invasive techniques prompts the need for the development of new biomaterials. Herein, we investigate the ability of Alginate incorporated with the fluorenylmethoxycarbonyl-diphenylalanine (FmocFF) peptide composite hydrogel to serve as a potential biomaterial for bone regeneration. We demonstrate that the incorporation of the self-assembling peptide, FmocFF, in sodium alginate leads to the production of a rigid, yet injectable, hydrogel without the addition of cross-linking agents. Scanning electron microscopy reveals a nanofibrous structure which mimics the natural bone extracellular matrix. The formed composite hydrogel exhibits thixotropic behavior and a high storage modulus of approximately 10 kPA, as observed in rheological measurements. The in vitro biocompatibility tests carried out with MC3T3-E1 preosteoblast cells demonstrate good cell viability and adhesion to the hydrogel fibers. This composite scaffold can induce osteogenic differentiation and facilitate calcium mineralization, as shown by Alizarin red staining, alkaline phosphatase activity and RT-PCR analysis. The high biocompatibility, excellent mechanical properties and similarity to the native extracellular matrix suggest the utilization of this hydrogel as a temporary three-dimensional cellular microenvironment promoting bone regeneration.


2011 ◽  
Vol 32 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Wenjing Zhao ◽  
Scott A. McCallum ◽  
Zhongping Xiao ◽  
Fuming Zhang ◽  
Robert J. Linhardt

Heparin and HS (heparan sulfate) exert their wide range of biological activities by interacting with extracellular protein ligands. Among these important protein ligands are various angiogenic growth factors and cytokines. HS binding to VEGF (vascular endothelial growth factor) regulates multiple aspects of vascular development and function through its specific interaction with HS. Many studies have focused on HS-derived or HS-mimicking structures for the characterization of VEGF165 interaction with HS. Using a heparinase 1-prepared small library of heparin-derived oligosaccharides ranging from hexasaccharide to octadecasaccharide, we systematically investigated the heparin-specific structural features required for VEGF binding. We report the apparent affinities for the association between the heparin-derived oligosaccharides with both VEGF165 and VEGF55, a peptide construct encompassing exclusively the heparin-binding domain of VEGF165. An octasaccharide was the minimum size of oligosaccharide within the library to efficiently bind to both forms of VEGF and a tetradecasaccharide displayed an effective binding affinity to VEGF165 comparable to unfractionated heparin. The range of relative apparent binding affinities among VEGF and the panel of heparin-derived oligosaccharides demonstrate that the VEGF binding affinity likely depends on the specific structural features of these oligosaccharides, including their degree of sulfation, sugar-ring stereochemistry and conformation. Notably, the unique 3-O-sulfo group found within the specific antithrombin binding site of heparin is not required for VEGF165 binding. These findings afford new insight into the inherent kinetics and affinities for VEGF association with heparin and heparin-derived oligosaccharides with key residue-specific modifications and may potentially benefit the future design of oligosaccharide-based anti-angiogenesis drugs.


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