Developing a Strontium-Releasing Graphene Oxide-/Collagen-Based Organic–Inorganic Nanobiocomposite for Large Bone Defect Regeneration via MAPK Signaling Pathway

2019 ◽  
Vol 11 (17) ◽  
pp. 15986-15997 ◽  
Author(s):  
Yahong Chen ◽  
Zhiwei Zheng ◽  
Renpeng Zhou ◽  
Huizhong Zhang ◽  
Chuhsin Chen ◽  
...  
2019 ◽  
Vol 20 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Qingcheng Liu ◽  
Yu Zhuang ◽  
Ningjuan Ouyang ◽  
Hongbo Yu

Background: Bone defect caused by trauma, tumor resection, infection or congenital malformation is a common clinical disease. Bone tissue engineering is regarded as a promising way of bone defect reconstruction. Thus, agents that can promote osteogenesis have received great attention. Cytochalasin D (Cyto D), a metabolite derived from molds, proves to be able to modify actin, reorganize cytoskeleton, and then promote the osteogenic differentiation. Objective: The purpose of this study was to explore the effect and mechanism of Cyto D on osteogenic differentiation of mouse pre-osteoblast MC3T3-E1 cells. Methods: The optimum concentration of Cyto D was explored. The osteogenic differentiation of MC3T3-E1 cells induced by Cyto D was assessed by alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, western blotting and quantitative real-time polymerase chain reaction (RT-qPCR). In addition, a specific pathway inhibitor was utilized to explore whether MAPK pathways were involved in this process. Results: The results showed that the optimized concentration of action was 10-2µg/ml. The expression of Runx2, OCN and OSX was up-regulated by the supplement of Cyto D. ALP activity, calcium deposition, and phosphorylation level of p38 protein were also improved. Inhibition of the pathway significantly reduced the activation of p38, and the expression of osteogenic-related genes. Conclusion: Cyto D can promote the osteogenic differentiation of MC3T3 cells via the p38-MAPK signaling pathway, but not the ERK1/2 or JNK, and it is a potential agent to improve the osteogenesis of MC3T3 cells.


2021 ◽  
Vol 12 ◽  
Author(s):  
Weipeng Sun ◽  
Minying Li ◽  
Lei Xie ◽  
Zhexing Mai ◽  
Yan Zhang ◽  
...  

Drynariae Rhizoma (DR) has been demonstrated to be effective in promoting fracture healing in clinical use. In the study, we tried to predicate potential signaling pathways and active ingredients of DR via network pharmacology, uncover its regulation mechanism to improve large bone defects by in vivo and in vitro experiment. We total discovered 18 potential active ingredients such as flavonoids and 81 corresponding targets, in which mitogen-activated protein kinase (MAPK) signaling pathway has the highest correlation with bone defects in pathway and functional enrichment analysis. Therefore, we hypothesized that flavonoids in DR improve large bone defects by activating MAPK signaling pathway. Animal experiments were carried out and all rats randomly divided into TFDR low, medium, and high dosage group, model group and control group. 12 weeks after treatment, according to X-ray and Micro-CT, TFDR medium dosage group significantly promote new bone mineralization compared with other groups. The results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFDR groups. Also, angiographic imaging suggested that flavonoids in DR promoting angiogenesis in the defect area. Consistently, TFDR significantly enhanced the expression of BMP-2, RUNX-2, VEGF, HIF-1 in large bone defect rats based on ELISA and Real-Time PCR. Overall, we not only discover the active ingredients of DR in this study, but also explained how flavonoids in DR regulating MAPK signaling pathway to improve large bone defects.


2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.


Neoplasia ◽  
2021 ◽  
Vol 23 (6) ◽  
pp. 607-623
Author(s):  
Hui Xu ◽  
Xiaomei Yang ◽  
Xiaofeng Xuan ◽  
Di Wu ◽  
Jieru Zhang ◽  
...  

2016 ◽  
Vol 33 ◽  
pp. 63-72 ◽  
Author(s):  
Yu-Chen Cheng ◽  
You-Ming Ding ◽  
Dueng-Yuan Hueng ◽  
Jang-Yi Chen ◽  
Ying Chen

2012 ◽  
Vol 33 (12) ◽  
pp. 1500-1505 ◽  
Author(s):  
Yu Sun ◽  
Shusheng Tang ◽  
Xi Jin ◽  
Chaoming Zhang ◽  
Wenxia Zhao ◽  
...  

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