scholarly journals Apigenin neutralizes the inhibitory effect of inflammation on the osteogenic differentiation of human mesenchymal stem cells

Abstract The authors have requested that this preprint be withdrawn due to author disagreement.

2021 ◽  
Author(s):  
Azita Asadi ◽  
Farjam Goudarzi ◽  
Mustafa Ghanadian ◽  
Adel Mohammadalipour

Abstract Background: The stimulating effects of apigenin on mesenchymal stem cells (MSCs) osteogenesis, as well as the anti-inflammatory effect of this flavonoid, have been identified. In this study, osteogenic differentiation was investigated under inflammatory conditions and treatment with apigenin. Methods and Results: Along with osteogenic differentiation of MSCs, they became inflamed with LPS/PA, and treated simultaneously with apigenin. The degree of differentiation was assessed by alizarin red staining and alkaline phosphatase (ALP) activity. Also, gene expression of NLRP3 and RUNX2 was performed along with protein expression of IL-1β. Significant increase in NLRP3 and IL-1β were observed in MSCs when exposed to LPS/PA (p<0.01). Also, the osteogenesis was significantly decreased (p<0.01). Apigenin treatment induced significantly higher gene expression of RUNX2, the activity of ALP, and cell staining (p<0.01) which were also associated with reduced inflammation in these cells. Conclusions: The effectiveness of apigenin on osteogenesis under inflammatory conditions was cautiously observed.


2019 ◽  
Author(s):  
Leiluo Yang ◽  
Qing Li ◽  
Junhong Zhang ◽  
Pengcheng Li ◽  
Chaoliang Wang ◽  
...  

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 927
Author(s):  
Ki-Taek Lim ◽  
Dinesh-K. Patel ◽  
Sayan-Deb Dutta ◽  
Keya Ganguly

Human mesenchymal stem cells (hMSCs) have the potential to differentiate into different types of mesodermal tissues. In vitro proliferation and differentiation of hMSCs are necessary for bone regeneration in tissue engineering. The present study aimed to design and develop a fluid flow mechanically-assisted cartridge device to enhance the osteogenic differentiation of hMSCs. We used the fluorescence-activated cell-sorting method to analyze the multipotent properties of hMSCs and found that the cultured cells retained their stemness potential. We also evaluated the cell viabilities of the cultured cells via water-soluble tetrazolium salt 1 (WST-1) assay under different rates of flow (0.035, 0.21, and 0.35 mL/min) and static conditions and found that the cell growth rate was approximately 12% higher in the 0.035 mL/min flow condition than the other conditions. Moreover, the cultured cells were healthy and adhered properly to the culture substrate. Enhanced mineralization and alkaline phosphatase activity were also observed under different perfusion conditions compared to the static conditions, indicating that the applied conditions play important roles in the proliferation and differentiation of hMSCs. Furthermore, we determined the expression levels of osteogenesis-related genes, including the runt-related protein 2 (Runx2), collagen type I (Col1), osteopontin (OPN), and osteocalcin (OCN), under various perfusion vis-à-vis static conditions and found that they were significantly affected by the applied conditions. Furthermore, the fluorescence intensities of OCN and OPN osteogenic gene markers were found to be enhanced in the 0.035 mL/min flow condition compared to the control, indicating that it was a suitable condition for osteogenic differentiation. Taken together, the findings of this study reveal that the developed cartridge device promotes the proliferation and differentiation of hMSCs and can potentially be used in the field of tissue engineering.


2021 ◽  
Vol 13 (6) ◽  
pp. 7051-7059
Author(s):  
Yingnan Zhang ◽  
Changhao Fang ◽  
Shuce Zhang ◽  
Robert E. Campbell ◽  
Michael J. Serpe

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fangzi Gong ◽  
Le Gao ◽  
Luyao Ma ◽  
Guangxin Li ◽  
Jianhong Yang

Abstract Background Progressive population aging has contributed to the increased global prevalence of diabetes and osteoporosis. Inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by hyperglycemia is a potential pathogenetic mechanism of osteoporosis in diabetic patients. Uncarboxylated osteocalcin (GluOC), a protein secreted by mature osteoblasts, regulates bone development as well as glucose and lipid metabolism. In our previous studies, GluOC was shown to promote osteoblastic differentiation of BMSCs; however, the underlying mechanisms are not well characterized. Tumor protein 63 (TP63), as a  transcription factor, is closely related to bone development and glucose metabolism. Results In this study, we verified that high glucose suppressed osteogenesis and upregulated adipogenesis in BMSCs, while GluOC alleviated this phenomenon. In addition, high glucose enhanced TP63 expression while GluOC diminished it. Knock-down of TP63 by siRNA transfection restored the inhibitory effect of high glucose on osteogenic differentiation. Furthermore, we detected the downstream signaling pathway PTEN/Akt/GSK3β. We found that diminishing TP63 decreased PTEN expression and promoted the phosphorylation of Akt and GSK3β. We then applied the activator and inhibitor of Akt, and concluded that PTEN/Akt/GSK3β participated in regulating the differentiation of BMSCs. Conclusions Our results indicate that GluOC reduces the inhibitory effect of high glucose on osteoblast differentiation by regulating the TP63/PTEN/Akt/GSK3β pathway. TP63 is a potential novel target for the prevention and treatment of diabetic osteoporosis.


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