scholarly journals Polyelectrolyte Complexes between Polycarboxylates and BMP-2 for Enhancing Osteogenic Differentiation: Effect of Chemical Structure of Polycarboxylates

Polymers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1327
Author(s):  
Masahiko Terauchi ◽  
Atsushi Tamura ◽  
Asato Tonegawa ◽  
Satoshi Yamaguchi ◽  
Tetsuya Yoda ◽  
...  

Bone morphogenetic protein 2 (BMP-2) has received considerable attention because of its osteoinductivity, but its use is limited owing to its instability and adverse effects. To reduce the dose of BMP-2, complexation with heparin is a promising approach, because heparin enhances the osteoinductivity of BMP-2. However, the clinical use of heparin is restricted because of its anticoagulant activity. Herein, to explore alternative polymers that show heparin-like activity, four polycarboxylates, poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(aspartic acid) (PAsp), and poly(glutamic acid) (PGlu), were selected and their capability to modulate the osteoinductivity of BMP-2 was evaluated. Dynamic light scattering indicated that these polycarboxylates formed polyelectrolyte complexes with BMP-2. The osteogenic differentiation efficiency of MC3T3-E1 cells treated with the polycarboxylate/BMP-2 complexes was investigated in comparison to that of the heparin/BMP-2 complex. As a result, PGlu/BMP-2 complex showed the highest activity of alkaline phosphatase, which is an early-stage marker of osteogenic differentiation, and rapid mineralization. Based on these observations, PGlu could serve as an alternative to heparin in the regenerative therapy of bone using BMP-2.

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Qin Lu ◽  
Yinan Liu ◽  
Yang Wang ◽  
Weiping Wang ◽  
Zhe Yang ◽  
...  

To investigate the effects of rapamycin on cardiac differentiation, murine embryonic stem cells (ESCs) were induced into cardiomyocytes by 10−4 M ascorbic acid (AA), 20 nM rapamycin alone or 0.01% solvent DMSO. We found that rapamycin alone was insufficient to initiate cardiomyogenesis. Then, the ESCs were treated with AA and rapamycin (20 nM) or AA and DMSO (0.01%) as a control. Compared with control, mouse ESCs (mESCs) treated with rapamycin (20 nM) and AA yielded a significantly higher percentage of cardiomyocytes, as confirmed by the percentage of beating embryonic bodies (EBs), the immunofluorescence and FACS analysis. Rapamycin significantly increased the expression of a panel of cardiac markers including Gata4, α-Mhc, β-Mhc, and Tnnt2. Additionally, rapamycin enhanced the expression of mesodermal and cardiac transcription factors such as Mesp1, Brachyury T, Eomes, Isl1, Gata4, Nkx2.5, Tbx5, and Mef2c. Mechanistic studies showed that rapamycin inhibits Wnt/β-catenin and Notch signaling but promotes the expression of fibroblast growth factor (Fgf8), Fgf10, and Nodal at early stage, and bone morphogenetic protein 2 (Bmp 2) at later stages. Sequential treatment of rapamycin showed that rapamycin promotes cardiac differentiation at the early and later stages. Interestingly, another mammalian target of rapamycin (mTOR) inhibitor Ku0063794 (1 µM) had similar effects on cardiomyogenesis. In conclusion, our results highlight a practical approach to generate cardiomyocytes from mESCs by rapamycin.


Nanoscale ◽  
2019 ◽  
Vol 11 (45) ◽  
pp. 21953-21963 ◽  
Author(s):  
Xiaowei Xu ◽  
Maolei Sun ◽  
Dandan Wang ◽  
Wenhuan Bu ◽  
Zilin Wang ◽  
...  

Bone morphogenetic protein-2 plasmid was encapsulated by polyethylenimine-modified porous silica nanoparticles, which promoted osteogenic differentiation and increased calcium deposition with the involvement of autophagy.


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