scholarly journals Bone marrow-derived mesenchymal stem cells ameliorate chronic high glucose-induced β-cell injury through modulation of autophagy

2015 ◽  
Vol 6 (9) ◽  
pp. e1885-e1885 ◽  
Author(s):  
K Zhao ◽  
H Hao ◽  
J Liu ◽  
C Tong ◽  
Y Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Cell Injury ◽  
Β Cell

scholarly journals Uncarboxylated osteocalcin alleviates the inhibitory effect of high glucose on osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by regulating TP63

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fangzi Gong ◽  
Le Gao ◽  
Luyao Ma ◽  
Guangxin Li ◽  
Jianhong Yang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
High Glucose ◽  
Bone Development ◽  
Inhibitory Effect ◽  
Osteoblastic Differentiation ◽  
Diabetic Patients ◽  
Mouse Bone Marrow

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.

HIGH GLUCOSE INDUCED BONE LOSS VIA ATTENUATING THE PROLIFERATION AND OSTEOBLASTOGENESIS AND ENHANCING ADIPOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS

2013 ◽  
Vol 25 (05) ◽  
pp. 1340010 ◽  
Author(s):  
Wen-Tyng Li ◽  
Wen-Kai Hu ◽  
Feng-Ming Ho
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
High Glucose ◽  
Chromatin Condensation ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Bone Marrow Mscs

Diabetes mellitus (DM) is associated with bone loss and leads to osteopenia and osteoporosis. This study was undertaken to investigate whether the impaired functions of mesenchymal stem cells (MSCs) derived from bone marrow play a role in pathogenesis of DM-associated bone loss. Bone marrow MSCs were taken from the alloxan-induced diabetic rats and normal rats. Bone mineral densities of tibias and femurs in diabetic rats decreased compared to those of normal rats as shown by dual energy X-ray absorptiometry. MSCs from diabetic rats exhibited reduced colony formation activity. The in vitro effects of high glucose (HG) (20 or 33 mM) on the growth, oxidative stress, apoptosis, and differentiation MSCs were next assessed. The viability and proliferation of MSCs derived from diabetic rats decreased significantly compared with that from normal rats. HG further suppressed the proliferation and viability of MSCs from both diabetic and normal rats. HG was associated with 38–40% increase in reactive oxygen species level and had significantly downregulated the activities of superoxide dismutase (SOD) and catalase (CAT) which could be recovered by the addition of L-ascorbic acid. The phenomena of apoptosis such as chromatin condensation and DNA fragmentation were found in cells cultured under HG conditions. As compared with 5.5 mM glucose, exposure of MSCs to HG enhanced adipogenic induction of triacylglycerol accumulation and inhibited osteogenic induction of alkaline phosphatase activity. HG increased peroxisome proliferator-activated receptor gamma expression during adipogenesis and reduced RUNX2 expression during osteoblastogenesis. These results indicate that MSCs derived from diabetic rats exhibited the inhibitory effects on cell growth and osteogenic ability. The oxidative stress, apoptosis, and adipogenic capability of MSCs were increased by HG. Furthermore, it is suggested that HG induces bone loss via attenuating the proliferation and osteoblastogenesis and enhancing adipogenesis mediated by the oxidative stress in rat bone marrow MSCs.

Effect of Substance P on Bone Marrow Mesenchymal Stem Cells Differentiation in High Glucose Environment

2020 ◽  
Vol 10 (2) ◽  
pp. 252-258
Author(s):  
HeTong Yu ◽  
Yanjun Li ◽  
Xiaowei Ren ◽  
Huanhuan Zhao ◽  
Chong Nan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Substance P ◽  
High Glucose ◽  
Mtor Signaling ◽  
Alp Activity ◽  
Ampk Phosphorylation ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) can be used to treat bone defects. The neuropeptide substance P (SP) plays an important role in a variety of life activities. However, the effect of SP on BMSCs differentiation in high glucose environment remains unclear. Rat BMSCs were isolated and divided into control group; high glucose group; and SP group. The secretion of SP was detected by ELISA; cell proliferation was detected by MTT assay; apoptosis activity was detected by Cas-pase3 activity kit. Real time PCR was performed to measure Bax and Bcl-2 expression. Alizarin red staining was to detect calcified nodule formation. Western blot was done to measure AMPK/mTOR signaling protein expression. In high glucose environment, SP secretion was significantly decreased, along with increased cell proliferation, Caspase3 activity and Bax expression. Meanwhile, Bcl-2 expression, ALP activity and calcified nodules formation was significantly decreased with reduced AMPK phosphorylation and increased mTOR expression (P < 0.05). SP addition in high glucose environment significantly promoted SP secretion and cell proliferation, decreased Caspase3 activity and Bax expression, increased Bcl-2 expression, ALP activity and calcification nodules formation with increased AMPK phosphorylation and decreased mTOR expression (P < 0.05). In high glucose environment, SP secretion is decreased in BMSCs. Up-regulation of SP in BMSCs cells in high glucose environment inhibit the apoptosis of BMSCs and promote cell proliferation and osteogenesis by regulating AMPK/mTOR signaling pathway.

High glucose inhibits osteogenic differentiation of bone marrow mesenchymal stem cells via regulating miR-493-5p/ZEB2 signalling

2020 ◽  
Vol 167 (6) ◽  
pp. 613-621
Author(s):  
Zhongshu Zhai ◽  
Wanhong Chen ◽  
Qiaosheng Hu ◽  
Xin Wang ◽  
Qing Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
High Glucose ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Downstream Target ◽  
Marrow Mesenchymal Stem Cells ◽  
Diabetic Osteoporosis

Abstract Diabetic osteoporosis (DOP) is attributed to the aberrant physiological function of bone marrow mesenchymal stem cells (BMSCs) under high glucose (HG) environment. MicroRNAs (miRNAs) are involved in the pathological processes of DOP. We aimed to explore the underlying mechanism of miRNA in DOP. BMSCs were cultured in osteogenic medium with HG to induce osteogenic differentiation, and the interaction between miR-493-5p and ZEB2 was assessed by luciferase assay. Herein, we found miR-493-5p is gradually reduced during osteogenic differentiation in BMSCs. HG treatment inhibits osteogenic differentiation and induces an up-regulation of miR-493-5p leading to reduced level of its downstream target ZEB2. Inhibition of miR-493-5p attenuates HG-induced osteogenic differentiation defects by upregulation of ZEB2. Mechanistically, miR-493-5p/ZEB2 signalling mediates HG-inhibited osteogenic differentiation by inactivation of Wnt/β-catenin signalling. More importantly, knockdown of miR-493-5p therapeutically alleviated the DOP condition in mice. HG prevents BMSCs osteogenic differentiation via up-regulation of miR-493-5p, which results in reduced level of ZEB2 by directly targeting its 3′-untranslated region of mRNA. Thus, miR-493-5p/ZEB2 is a potential therapeutic target and provides novel strategy for the treatment and management of DOP.

Bone marrow-derived mesenchymal stem cells co-cultured with pancreatic islets display β cell plasticity

2010 ◽  
Vol 5 (6) ◽  
pp. 491-500 ◽  
Author(s):  
Erdal Karaoz ◽  
Selda Ayhan ◽  
Alparslan Okçu ◽  
Ayça Aksoy ◽  
Gülay Bayazıt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Pancreatic Islets ◽  
Cell Plasticity ◽  
Β Cell

281 USE OF MESENCHYMAL STEM CELLS COLLECTED FROM BONE MARROW OF ADULT DOGS FOR THE TREATMENT OF NON-UNION BONE FRACTURES

2008 ◽  
Vol 20 (1) ◽  
pp. 220
Author(s):  
C. B. Dores ◽  
J. F. Lima-Neto ◽  
O. C. M. Pereira-Junior ◽  
T. S. Rascado ◽  
D. Passarelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
High Glucose ◽  
Bone Fractures ◽  
Fibrous Tissue ◽  
Fracture Site ◽  
Non Union ◽  
Fracture Stabilization

The mesenchymal stem cells (MSC) are multipotent cells present in the bone marrow. The plasticity of these cells allows them to be used in cell therapy since they have the potential to replicate as undifferentiated cells and can be induced to differentiate into bone, fat, cartilage, tendon, muscle, and other tissues. The establishment of a pattern to culture MSC is the first step to start further experiments including MSC differentiation, cell therapy, and autologous transplants. In the present study, three dogs presenting non-union bone fractures, with one to two years of evolution, one in the middle third of the femur and the other two on the distal third of the radius and the ulna, were submitted to stem cell transplantation. After general anesthesia (IV) MSCs were aspirated from the head of the humerus from each dog and centrifuged at 1500 rpm for 10 minutes to eliminate the serum and the fat. The material was resuspended in a 1/1 proportion with DMEM High Glucose (GIBCO, Grand Island, NY, USA) and centrifuged with 7 mL of Ficoll-Paque (density 1.077 g mL–1; Amersham Biosciences, Sao Paulo, Brazil) at 1500 rpm for 40 min. The middle ring formed was aspirated and washed in DMEM High Glucose. The pellet was resuspended in DMEM High glucose with 20% fetal calf serum, penicillin, amphotericin B, and streptomycin. Primary cultures were established and subcultivated for as many as 4 passages. MSCs were cultured in humidified incubators with 5% CO2 in air and allowed to adhere for 120 h, followed by media change every 3 to 4 days. When cultures reached more than 90% confluence, adherent cells were detached with 0.05% trypsin-EDTA (GIBCO) and replanted (passage) at a density of 2 � 106 per 175 cm2 flask. To confirm the lineage of the MSCs, anti-vimentin immunocytochemistry was performed. After about 15 days of culture the cells were resuspended at a concentration of 2 � 107 cells mL–1 and prepared for transfer. The animals were subjected to a surgical procedure where the metallic implant (n = 3) and the fibrous tissue present in the non-union fracture site were removed and the fracture was stabilized with the use of steel bone plate and screws. At the end of the fracture stabilization, the cells were transferred directly into the fracture site. Radiographic exams were performed on the post-surgical site immediately after the surgery and monthly until complete bone healing, which was considered satisfactory 5 to 8 months after the surgery in all animals. The clinical results indicate that the therapy with homologous mesenchymal stem cells is a promising and efficient method to treat non-union bone fractures in dogs. This work was supported by FAPESP (grants 06/54575-0 and 06/56738-4).

Resveratrol reverses myogenic induction supression caused by high glucose through activating SIRT1/AKT/FOXO1 pathway

2020 ◽  
Author(s):  
Meiling Liu(Former Corresponding Author) ◽  
Luyang Cheng ◽  
Xianglu Li ◽  
Haifeng Ding ◽  
Hongzhi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
High Glucose ◽  
Myogenic Differentiation ◽  
Therapeutic Effects ◽  
Sod Activity ◽  
Marrow Mesenchymal Stem Cells ◽  
Myogenic Induction

Abstract Background: Long-term high glucose environment can cause muscle tissue atrophy, and then lead to musculoskeletal depression or even disability. Regenerative medicine is an extremely attractive select to solve this problem. Resveratrol is a compound which has various clinical therapeutic effects including regulating the myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). So, the objective of this study is to observe if resveratrol affect myogenic induction of rat BMSCs under high glucose environment and explore the possible mechanism. Methods: Rat BMSCs were isolated and cultured. The phenotypes were identified when cultured to the third passage cells (P3 cells). Then the P3 cells were used to induce to differentiate into myogenic cells by using the conditioned medium. After grouping, glucose, resveratrol and EX527 (inhibitor of SIRT1) were added. The cell viability was measured by MTT assay. The myogenesis related protein was detected by immunofluorescence. The level of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity were detected by use of assay kits. The cell cycle was assayed with flow cytometry. The expression of FOXO1, AKT, p-AKT, MyoD1 and Myogenin were measured by WB. All above indicators in different groups were quantified and compared. Results: During myogenic induction, after 72h treatment, high glucose (35 mmol/L) reduced cell viability and proliferation of rat BMSCs significantly, increased intracellular ROS levels clearly, decreased SOD activity obviously, and restrained AKT/FOXO1 pathway apparently. Resveratrol (15μmol/L) could regulate the process positively and reverse the suppression caused by high glucose partly through restoring cell proliferation and viability, reducing peroxidative damage and activating AKT/FOXO1 pathway. After pretreated the cells with EX527 (20 μmol/L), this reverse effect of resveratrol was eliminated. Conclusion: Resveratrol not only promoted myogenic induction of rat BMSCs, but also partially reversed myogenic induction supression of rat BMSCs caused by high glucose through activating SIRT1/AKT/FOXO1 pathway. [Key words] resveratrol, bone marrow mesenchymal stem cells, myogenic induction, glucose, SIRT1, AKT, FOXO1

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