Osteogenic differentiation of mesenchymal stem cells modulated by a chemically modified super-hydrophilic titanium implant surface

2018 ◽  
Vol 33 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Yong-Su Kwon ◽  
Jin-Woo Park

This study investigated the osteogenic functionality of multipotent mesenchymal stem cells (MSCs) modulated by a chemically modified super-hydrophilic titanium (Ti) bone implant surface to elucidate the biological mechanism underlying the bone healing capacity of this modified Ti surface. A microstructured Ti surface incorporating bioactive ions (in this study, phosphate (P) ions) was prepared by wet chemical treatment. The results showed that the hydrothermally obtained crystalline P-incorporated Ti surface (P surface) displayed long-term super-hydrophilicity (water contact angles <5°) during a 36-week observation period. The hydrophilic P surface enhanced early cellular functions and osteogenic differentiation of multipotent MSCs derived from mouse bone marrow and human adipose tissue. The expression of critical integrins affecting subsequent osteoblast function and osteoblast phenotype genes was notably upregulated in multipotent MSCs grown on the P surface compared with the commercially available grit-blasted microrough clinical oral implant surface. The P surface supported better cell spreading, focal adhesion and ALP activity of MSCs. These results indicate that a super-hydrophilic P-incorporated Ti surface accelerates implant bone healing by enhancing the early osteogenesis functions of multipotent MSCs.

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.


2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Jin-Woo Park ◽  
Yusuke Tsutsumi ◽  
Eui-Kyun Park

The manganese (Mn) ion has recently been probed as a potential candidate element for the surface chemistry modification of titanium (Ti) implants in order to develop a more osteogenic surface with the expectation of taking advantage of its strong binding affinity to the integrins on bone-forming cells. However, the exact mechanism of how Mn enhances osteogenesis when introduced into the surface of Ti implants is not clearly understood. This study investigated the corrosion resistance and potential osteogenic capacity of a Mn-incorporated Ti surface as determined by electrochemical measurement and examining the behaviors of human mesenchymal stem cells (MSCs) in a clinically available sandblasted/acid-etched (SLA) oral implant surface intended for future biomedical applications. The surface that resulted from wet chemical treatment exhibited the formation of a Mn-containing nanostructured TiO2 anatase thin film in the SLA implant and improved corrosion resistance. The Mn-incorporated SLA surface displayed sustained Mn ion release and enhanced osteogenesis-related MSC function, which enhanced early cellular events such as spreading, focal adhesion, and mRNA expression of critical adhesion-related genes and promoted full human MSC differentiation into mature osteoblasts. Our findings indicate that surface Mn modification by wet chemical treatment is an effective approach to produce a Ti implant surface with increased osteogenic capacity through the promotion of the osteogenic differentiation of MSCs. The improved corrosion resistance of the resultant surface is yet another important benefit of being able to provide favorable osseointegration interface stability with an increased barrier effect.


Author(s):  
Sabine Neuss ◽  
Claudia Panfil ◽  
Daniela Filipa Duarte Campos ◽  
Michael Weber ◽  
Christian Otten ◽  
...  

AbstractSeveral studies focusing on bone tissue engineering demonstrated that given microstructuring of an implant surface has a strong effect on its interaction with cells, and their adhesion and differentiation. In the present study, geometrically structured titanium alloy surfaces are shown to be able to guide cell adhesion during differentiation


2010 ◽  
Vol 638-642 ◽  
pp. 600-605 ◽  
Author(s):  
Frank Lüthen ◽  
Claudia Bergemann ◽  
Ulrike Bulnheim ◽  
Cornelia Prinz ◽  
Hans Georg Neumann ◽  
...  

To stimulate bone regeneration, the design of bioactive implants is a great challenge in current orthopedic research. We reasoned that implants should be suitable both to stimulate osteogenic differentiation of mesenchymal stem cells and prevent infections at the site of implantation. Therefore, we focus on copper ions, which are known to exert antimicrobial effects. On the other hand, copper is essential for the cell physiology, including the formation of the extracellular matrix. We studied the influence of copper ions on mesenchymal stem cells at various concentrations and identified the limits of copper concentrations for cell survival. Below the critical concentration for cell survival we analysed proliferation and osteogenic differentiation of the cells in the presence of copper ions. We found that copper stimulated the proliferation of the mesemchymal stem cells at 0.1 mM. Osteogenic differentiation decreased after 14 days at a concentration of 0.05 - 0.1 mM copper ions in osteogenic medium measured by the expression of osteogenic proteins, like alkaline phosphatase (ALP), bone sialoprotein (BSP) and collagen I (COL). We argue that at the implant surface a higher concentration of copper could prevent biofilm formation of bacteria and physiological concentrations in the vicinity of the implant would stimulate stem cell expansion. Together, copper is an interesting agent to control both bacteria and stem cells in the field of implant technology.


Author(s):  
Fengjie Li ◽  
Rong Zhang ◽  
Changpeng Hu ◽  
Qian Ran ◽  
Yang Xiang ◽  
...  

PurposeRepairing the irradiation-induced osteogenic differentiation injury of bone marrow mesenchymal stem cells (BM-MSCs) is beneficial to recovering haematopoiesis injury in radiotherapy; however, its mechanism is elusive. Our study aimed to help meet the needs of understanding the effects of radiotherapy on BM-MSC osteogenic potential.Methods and MaterialsBalb/c mice and the BM-MSCs were used to evaluate the irradiation-induced osteogenic differentiation injury in vivo. The cellular and molecular characterization were applied to determine the mechanism for recovery of irradiation-derived haematopoiesis injuries.ResultsWe report a functional role of IL-12 in acute irradiation hematopoietic injury recovery and intend to dissect the possible mechanisms through BM-MSC, other than the direct effect of IL-12 on hematopoietic stem and progenitor cells (HSPCs). Specifically, we show that early use of IL-12 enhanced the osteogenic differentiation of BM-MSCs through IL-12Rβ1/TYK2/STAT3 signaling; furthermore, IL-12 induced osteogenesis facilitated bone formation and irradiation hematopoiesis recovery when transplanted BM-MSCs in the femur of Balb/c mice. For the mechanism of action, we found that IL-12 receptor beta 1 (IL-12Rβ1) expression of irradiated BM-MSCs was upregulated rapidly, coincidentally consistent with early use of IL-12 induced osteogenic differentiation enhancement. IL-12Rβ1 and tyrosine kinase 2 gene (Tyk2) silencing experiments and phosphotyrosine of signal transducer and activator of transcription 3 (p-STAT3) suppression experiments indicated the IL-12Rβ1/TYK2/STAT3 signaling was essential in IL-12-induced osteogenic differentiation enhancement of BM-MSCs.ConclusionThese findings suggested that IL-12 may exert BM-MSCs-based hematopoietic recovery by repairing osteogenic differentiation abilities damages through IL-12Rβ1/TYK2/STAT3 signaling pathway post-irradiation.


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