scholarly journals Effect of silver nanoparticles on human mesenchymal stem cell differentiation

2014 ◽  
Vol 5 ◽  
pp. 2058-2069 ◽  
Author(s):  
Christina Sengstock ◽  
Jörg Diendorf ◽  
Matthias Epple ◽  
Thomas A Schildhauer ◽  
Manfred Köller
Keyword(s):  
Silver Nanoparticles ◽  
Cell Differentiation ◽  
Osteogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Laser Scanning Microscopy ◽  
Surgical Instruments ◽  
Dependent Manner ◽  
Low Concentration ◽  
Long Term Treatment

Background: Silver nanoparticles (Ag-NP) are one of the fastest growing products in nano-medicine due to their enhanced antibacterial activity at the nanoscale level. In biomedicine, hundreds of products have been coated with Ag-NP. For example, various medical devices include silver, such as surgical instruments, bone implants and wound dressings. After the degradation of these materials, or depending on the coating technique, silver in nanoparticle or ion form can be released and may come into close contact with tissues and cells. Despite incorporation of Ag-NP as an antibacterial agent in different products, the toxicological and biological effects of silver in the human body after long-term and low-concentration exposure are not well understood. In the current study, we investigated the effects of both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan. Results: As shown through laser scanning microscopy, Ag-NP with a size of 80 nm (hydrodynamic diameter) were taken up into hMSCs as nanoparticulate material. After 24 h of incubation, these Ag-NP were mainly found in the endo-lysosomal cell compartment as agglomerated material. Cytotoxicity was observed for differentiated or undifferentiated hMSCs treated with high silver concentrations (≥20 µg·mL−1 Ag-NP; ≥1.5 µg·mL−1 Ag+ ions) but not with low-concentration treatments (≤10 µg·mL−1 Ag-NP; ≤1.0 µg·mL−1 Ag+ ions). Subtoxic concentrations of Ag-NP and Ag+ ions impaired the adipogenic and osteogenic differentiation of hMSCs in a concentration-dependent manner, whereas chondrogenic differentiation was unaffected after 21 d of incubation. In contrast to aggrecan, the inhibitory effect of adipogenic and osteogenic differentiation was confirmed by a decrease in the secretion of specific biomarkers, including adiponectin (adipocytes) and osteocalcin (osteoblasts). Conclusion: Aside from the well-studied antibacterial effect of silver, little is known about the influence of nano-silver on cell differentiation processes. Our results demonstrate that ionic or nanoparticulate silver attenuates the adipogenic and osteogenic differentiation of hMSCs even at non-toxic concentrations. Therefore, more studies are needed to investigate the effects of silver species on cells at low concentrations during long-term treatment.

scholarly journals Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

scholarly journals Bacterial flagella as an osteogenic differentiation nano-promoter

2019 ◽  
Vol 4 (6) ◽  
pp. 1286-1292 ◽  
Author(s):  
Dong Li ◽  
Ye Zhu ◽  
Tao Yang ◽  
Mingying Yang ◽  
Chuanbin Mao
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Osteogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Osteogenic Medium ◽  
Bacterial Flagella

Flagella detached from the surface of bacteria can promote stem cell differentiation in osteogenic medium.

scholarly journals Long-term therapeutic effect of vitamin D analog doxercalciferol on diabetic nephropathy: strong synergism with AT1 receptor antagonist

2009 ◽  
Vol 297 (3) ◽  
pp. F791-F801 ◽  
Author(s):  
Yan Zhang ◽  
Dilip K. Deb ◽  
Juan Kong ◽  
Gang Ning ◽  
Yurong Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Combination Therapy ◽  
Therapeutic Effect ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Filtration Barrier ◽  
Vitamin D Analog ◽  
Long Term Treatment

The intrarenal renin-angiotensin system (RAS) plays a key role in the development of diabetic nephropathy. Recently, we showed that combination therapy with an AT1 receptor blocker (ARB) and an activated vitamin D analog produced excellent synergistic effects against diabetic nephropathy, as a result of blockade of the ARB-induced compensatory renin increase. Given the diversity of vitamin D analogs, here we used a pro-drug vitamin D analog, doxercalciferol (1α-hydroxyvitamin D2), to further test the efficacy of the combination strategy in long-term treatment. Streptozotocin-induced diabetic DBA/2J mice were treated with vehicle, losartan, doxercalciferol (0.4 and 0.6 μg/kg), or losartan and doxercalciferol combinations for 20 wk. Vehicle-treated diabetic mice developed progressive albuminuria and glomerulosclerosis. Losartan alone moderately ameliorated kidney injury, with renin being drastically upregulated. A similar therapeutic effect was seen with doxercalciferol alone, which markedly suppressed renin and angiotensinogen expression. The losartan and doxercalciferol combination most effectively prevented albuminuria, restored glomerular filtration barrier structure, and dramatically reduced glomerulosclerosis in a dose-dependent manner. These effects were accompanied by blockade of intrarenal renin upregulation and ANG II accumulation. These data demonstrate an excellent therapeutic potential for doxercalciferol in diabetic renal disease and confirm the concept that blockade of the compensatory renin increase enhances the efficacy of RAS inhibition and produces synergistic therapeutic effects in combination therapy.

scholarly journals Long-Term Metformin Effect on Endometrial Cancer Development Depending on Glucose Environment in vitro

2020 ◽  
Author(s):  
Amanda Machado Weber ◽  
Carsten Lange ◽  
Julia Jauckus ◽  
Thomas Strowitzki ◽  
Ariane Germeyer
Keyword(s):  
Endometrial Cancer ◽  
Type I ◽  
Dependent Manner ◽  
Metabolic Disturbances ◽  
Concentration Dependent Manner ◽  
Estrogen Exposure ◽  
Long Term Treatment ◽  
And Migration

Abstract Background: The incidence of endometrial cancer has increased worldwide over the past years. Common risk factors include obesity and metabolic disturbances, like hyperinsulinemia and insulin resistance, as well as prolonged and elevated estrogen exposure. Metformin, an anti-hyperglycemic and insulin-sensitizing biguanide, displayed anti-proliferative effects in recent studies. Therefore, metformin may act as a therapeutic and prophylactic anti-cancer agent in several tissues, including endometrium. Methods: Two different endometrial cancer cell lines, reflecting type I (Ishikawa) and type II endometrial cancer (HEC-1A) were cultured under normoglycemic (5.5mM) or hyperglycemic (17.0mM) conditions and treated with different concentrations of metformin (0.01–5.0mM). Results: Effects of metformin on proliferation, cell viability, clonogenicity and migration were investigated after treatment for 7d. Long-term treatment with metformin showed effects on cellular viability, proliferation and migration of endometrial cancer cells in a concentration- dependent manner in vitro. Additionally, glucose levels affected the outcome of the experiments. Conclusion: Our in vitro findings support the hypothesis that metformin has a direct effect on endometrial tissues and reflects the importance of the local glucose environment, suggesting that metformin may be considered as a potential adjuvant agent in endometrial cancer therapy due to its direct and indirect effects on endometrial development.

Dual Effects of Intravenous Anesthetics on the Function of Norepinephrine Transporters

2000 ◽  
Vol 93 (5) ◽  
pp. 1329-1335 ◽  
Author(s):  
Koji Hara ◽  
Nobuyuki Yanagihara ◽  
Kouichiro Minami ◽  
Hideyasu Hirano ◽  
Takeyoshi Sata ◽  
...  
Keyword(s):  
Term Treatment ◽  
Scatchard Analysis ◽  
Dependent Manner ◽  
Short Term Treatment ◽  
Intravenous Anesthetics ◽  
Norepinephrine Uptake ◽  
Long Term Treatment ◽  
Desipramine Binding ◽  
Neuronal Transmission

Background Norepinephrine transporters (NETs) terminate the neuronal transmission of norepinephrine, which is released from noradrenergic neurons. To investigate the interaction with NET, the authors examined the effects of short- and long-term treatment with anesthetics on the activity and mRNA level of NET. Methods To assay [3H]norepinephrine uptake, bovine adrenal medullary cells in culture were incubated with [3H]norepinephrine in the presence of intravenous anesthetics, including propofol, thiamylal, and diazepam. To study the direct interaction between the anesthetics and NET, the effect of propofol on the binding of [3H]desipramine to the plasma membrane was examined. To study the long-term effect of anesthetics, [3H]norepinephrine uptake by cells pretreated with propofol for 6-24 h and [3H]desipramine binding after pretreatment for 12 h were measured. Simultaneously, we examined the effect of anesthetics on the expression of NET mRNA using the reverse transcriptase-polymerase chain reaction. Results All of the intravenous anesthetics inhibited [3H]norepinephrine uptake in a concentration-dependent manner. The active concentrations of propofol (1-3 microm) and thiamylal (< or = 30 microm) were similar to those encountered clinically. The kinetic analysis revealed that all the anesthetics noncompetitively inhibited [3H]norepinephrine uptake. Propofol inhibited [3H]desipramine binding with a potency similar to that observed in [3H]norepinephrine uptake. Scatchard analysis showed that propofol competitively inhibited [3H]desipramine binding. On the other hand, long-term treatment of cells with propofol (10 microm) enhanced the NET functional activity and [3H]desipramine binding, and also increased the level of NET mRNA. Conclusions These results suggest that intravenous anesthetics have a dual effect on NET; short-term treatment causes inhibition, whereas long-term treatment leads to up-regulation. The interaction of intravenous anesthetics with NET may modulate the neuronal transmission of norepinephrine during anesthesia.

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