Extracellular signal-regulated kinase1/2 activated by fluid shear stress promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through novel signaling pathways

2011 ◽  
Vol 43 (11) ◽  
pp. 1591-1601 ◽  
Author(s):  
Liyue Liu ◽  
Lan Shao ◽  
Bo Li ◽  
Chen Zong ◽  
Jianhu Li ◽  
...  
2019 ◽  
Vol 121 (3) ◽  
pp. 344-353 ◽  
Author(s):  
Mohamed I. Elashry ◽  
Shumet T. Gegnaw ◽  
Michele C. Klymiuk ◽  
Sabine Wenisch ◽  
Stefan Arnhold

2021 ◽  
Author(s):  
Mohamed I. Elashry ◽  
Nadine Baulig ◽  
Alena-Svenja Wagner ◽  
Michele C. Klymiuk ◽  
Benjamin Kruppke ◽  
...  

Abstract Background: Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose derived MSCs morphology, viability, adherence, migration and osteogenic differentiation.Methods: MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or mechanical fluid shear stress (FSS) culture conditions. The data were generated by histological means, live cell imaging, cell viability, adherence and migration assays, semi-quantification of alkaline phosphatase (ALP) activity and quantification of the osteogenic markers runt related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) expression.Results: The data revealed that combined mechanical FSS with MC but not B30 enhanced MSCs viability and promoted their migration. Combined osteogenic medium with MC, B30 and B30Str increased ALP activity compared to cultivation in basal medium. Osteogenic induction with MC, B30 and B30Str resulted in diffused matrix mineralization. The combined osteogenic induction with biomaterials under mechanical FSS increased Runx2 protein expression either in comparison to those cells cultivated in BM or those cells induced under static culture. Runx2 and ALP expression was upregulated following combined osteogenic differentiation together with B30 and B30Str regardless of static or FSS culture.Conclusions: Taken together, the data revealed that FSS in conjunction with biomaterials promoted osteogenic differentiation of MSCs. This combination may be considered as a marked improvement for clinical applications to cure bone defects.


2018 ◽  
Author(s):  
Linyuan Wang ◽  
Fang Xiao ◽  
Lei Yu ◽  
Hang Su ◽  
Yueqin Yang ◽  
...  

AbstractObjectiveBone marrow cells encounter various chemical and mechanical stimuli from the internal environment. In vivo, fluid shear stress (FSS) is one of the primary mechanical stimuli that affect bone marrow-derived mesenchymal stem cells (BMCs) activity. Since various cases of FSS influence BMCs activity differently, the purpose of this study is to determine how BMC activity in osteogenesis and osteoclastgenesis is affected by stable and unstable changing FSS.MethodBMCs samples from the femur of the mouse, divided in to three groups: stimulate by stable changing FSS, unstable changing FSS, and no FSS. RT-PCR would be applied to detect OPG, RANKL, ALP, OCN, RUNX2, and RANK of all the samples at the 3rd day. Alizarin red staining and TRAP staining would be applied to test all the samples at the 6th day.ResultsThe S group samples showed the lowest level in RANKL mRNA and showed the highest level in OPG mRNA. RANKL/OPG mRNA in the S group was the smallest during three groups. Comparing with the C group samples, RUNX2 mRNA in the S group was increased significantly. RANK mRNA in the C group was three times more than S group. S group had the largest area of mineralized nodules, and largest number of area ≥100µm, ≥500µm2 or ≥1000µm2. The area of positive TRAP stain in S group was the smallest among three groups.ConclusionStable changing FSS significantly increases osteogenesis relating to OPG-RANKL-RANK pathway. Compared with unstable changing FSS, stable changing FSS afford a more appropriate stimulation to osteogenesis.AbbreviationsALPAlkaline phosphataseBMCsBone marrow-derived mesenchymal stem cellsCx43Connexin 43C3aComplement Component 3aJNKc-Jun N-terminal kinaseERKExtracellular regulated protein kinasesERK5Extracellular-signal-regulated kinaseFSSFluid shear stressFasLFirst apoptosis signal LigandGSK3βGlycogen synthase kinase 3βLPALysophosphatidic acidMSCsMesenchymal stem cellsM-CSFMacrophage colony-stimulating factorMCP-1Monocyte chemoattractant protein-1RANKReceptor Activator of Nuclear Factor κ BRANKLReceptor activator of nuclear factor κ B ligandRUNX2Runt-related transcription factor 2P2Y2RReceptor of P2Y2LGR4Repeat-containing G-protein-coupled receptor 4SemaSemaphorinsTRAPTartrate-Resistant Acid AhosphataseTRPM7Transient receptor potential cation channel subfamily M member 7TRAFsTumornecrosisfactorreceptor associatedfactorsOPGOsteoprotegerinOCNOsteocalcinOPNOsteopontin


2021 ◽  
Vol 22 (6) ◽  
pp. 3123
Author(s):  
Sebastian Reiprich ◽  
Elif Akova ◽  
Attila Aszódi ◽  
Veronika Schönitzer

During biomineralization, the cells generating the biominerals must be able to sense the external physical stimuli exerted by the growing mineralized tissue and change their intracellular protein composition according to these stimuli. In molluscan shell, the myosin-chitin synthases have been suggested to be the link for this communication between cells and the biomaterial. Hyaluronan synthases (HAS) belong to the same enzyme family as chitin synthases. Their product hyaluronan (HA) occurs in the bone and is supposed to have a regulatory function during bone regeneration. We hypothesize that HASes’ expression and activity are controlled by fluid-induced mechanotransduction as it is known for molluscan chitin synthases. In this study, bone marrow-derived human mesenchymal stem cells (hMSCs) were exposed to fluid shear stress of 10 Pa. The RNA transcriptome was analyzed by RNA sequencing (RNAseq). HA concentrations in the supernatants were measured by ELISA. The cellular structure of hMSCs and HAS2-overexpressing hMSCs was investigated after treatment with shear stress using confocal microscopy. Fluid shear stress upregulated the expression of genes that encode proteins belonging to the HA biosynthesis and bone mineralization pathways. The HAS activity appeared to be induced. Knowledge about the regulation mechanism governing HAS expression, trafficking, enzymatic activation and quality of the HA product in hMSCs is essential to understand the biological role of HA in the bone microenvironment.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mohamed I. Elashry ◽  
Nadine Baulig ◽  
Alena-Svenja Wagner ◽  
Michele C. Klymiuk ◽  
Benjamin Kruppke ◽  
...  

Abstract Background Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose-derived MSC morphology, viability, adherence, migration, and osteogenic differentiation. Methods MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or mechanical fluid shear stress (FSS) culture conditions. The data were generated by histological means, live cell imaging, cell viability, adherence and migration assays, semi-quantification of alkaline phosphatase (ALP) activity, and quantification of the osteogenic markers runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) expression. Results The data revealed that combined mechanical FSS with MC but not B30 enhanced MSC viability and promoted their migration. Combined osteogenic medium with MC, B30, and B30Str increased ALP activity compared to cultivation in basal medium. Osteogenic induction with MC, B30, and B30Str resulted in diffused matrix mineralization. The combined osteogenic induction with biomaterials under mechanical FSS increased Runx2 protein expression either in comparison to those cells cultivated in BM or those cells induced under static culture. Runx2 and ALP expression was upregulated following combined osteogenic differentiation together with B30 and B30Str regardless of static or FSS culture. Conclusions Taken together, the data revealed that FSS in conjunction with biomaterials promoted osteogenic differentiation of MSCs. This combination may be considered as a marked improvement for clinical applications to cure bone defects.


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