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.

Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dkk1 to activate Wnt/β-catenin pathway

2020 ◽  
Author(s):  
Zhi Peng ◽  
Zhenkai Lou ◽  
Zhongjie Li ◽  
Shaobo Li ◽  
Kaishun Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Osteogenic Differentiation ◽  
Osteoblast Differentiation ◽  
Negative Regulator ◽  
Luciferase Assay ◽  
Alizarin Red ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has attracted attention in the field of bone remodeling. Methods: The exosomes were extracted from BMSCs and labeled by PKH-67, and then incubated with hFOB1.19 cells to investigate the miR-196a function on the osteoblast differentiation of hFOB1.19. The osteoblast differentiation was detected via alizarin red staining and the expression of osteoblast genes were detected by western blot. The cell apoptosis was detected by flow cytometer. The target relationship of miR-196a and Dickkopf-1 (Dkk1) were verified by luciferase assay and western blot. Results: Here we demonstrated that exosomes extracted from BMSCs (BMSC-exo) significantly promoted hFOB1.19 differentiation to osteoblasts. We found that BMSC-exo were enriched with miR-196a and delivered miR-196a to hFOB1.19 cells to inhibit its target Dkk1, which is a negative regulator of Wnt/β-catenin pathway. Conclusion: BMSC-exo activated Wnt/β-catenin pathway to promote osteogenic differentiation, while BMSC-exo failed to exert the effects when miR-196a was deprived. In conclusion, miR-196a delivered by exosomes from BMSCs plays an essential role in enhancing osteoblastic differentiation by targeting Dkk1 to activate Wnt/β-catenin pathway.

scholarly journals Semaphorin3B Promotes Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in a High-Glucose Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Quan Xing ◽  
Jingyi Feng ◽  
Xiaolei Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Metabolism ◽  
High Glucose ◽  
Bone Diseases ◽  
Akt Pathway ◽  
Bone Formation Markers ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) play an essential role in osteogenesis and bone metabolism and have already been recognized as one of the most popular seed cells for bone tissue engineering for bone diseases. However, high-glucose (HG) conditions in type 2 diabetes mellitus (T2DM) exert deleterious effects on BMSC proliferation and osteogenic differentiation. Semaphorin 3B (Sema3B) increases osteoblast differentiation in bone metabolism. Here, we determined the role of Sema3B in the proliferation and osteogenic differentiation of BMSCs in the HG microenvironment. The HG microenvironment decreased Sema3B expression in BMSCs. Moreover, HG inhibited BMSC proliferation. Furthermore, HG inhibited osteogenic differentiation in BMSCs by decreasing the expression of bone formation markers, alkaline phosphatase (ALP) activity, and mineralization. However, the administration of recombinant Sema3B reversed all of these effects. Moreover, our study found that Sema3B could activate the Akt pathway in BMSCs. Sema3B rescues defects in BMSC proliferation and osteogenic differentiation in the HG microenvironment by activating the Akt pathway. These effects were significantly reduced by treatment with an Akt inhibitor. Together, these findings demonstrate that Sema3B promotes the proliferation and osteogenic differentiation of BMSCs via the Akt pathway under HG conditions. Our study provides new insights into the potential ability of Sema3B to ameliorate BMSC proliferation and osteogenic differentiation in an HG microenvironment.

Tilianin Promotes the Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

2021 ◽  
Vol 20 (2) ◽  
pp. 259-264
Author(s):  
Zhixing Xue ◽  
Jin Yang ◽  
Panfeng Yu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
High Glucose ◽  
Flavonoid Glycoside ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Marrow Mesenchymal Stem Cells

Osteoporosis is a systemic bone disease characterized by a decrease in bone mineral density and mass. To examine the mechanism(s) underlying the pathogenesis of osteoporosis, we have used an in vitro model of osteoporosis induced by exposure to high glucose. Tilianin is a flavonoid glycoside isolated from Dracocephalum moldavica L. that has been reported to exhibit a variety of pharmacologic activities. However, the utility of tilianin in the treatment of osteoporosis remains unexplored. To this end, we have examined the effect of tilianin on bone marrow mesenchymal stem cells exposed to high glucose. Our data revealed that tilianin suppressed apoptosis, promoted osteogenic differentiation, and survival of the bone marrow mesenchymal stem cells in the presence of high glucose. Our data therefore confirmed that tilianin could serve as a promising drug for the treatment of osteoporosis.

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