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.

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.

scholarly journals miR-206 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells by targetting glutaminase

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Ying Chen ◽  
Yu-Run Yang ◽  
Xiao-Liang Fan ◽  
Peng Lin ◽  
Huan Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Osteoblast Differentiation ◽  
Bone Diseases ◽  
Glutamine Metabolism ◽  
Mrna Levels ◽  
Marrow Mesenchymal Stem Cells ◽  
Osteogenic Induction

AbstractOsteoblast-mediated bone formation is a complex process involving various pathways and regulatory factors, including cytokines, growth factors, and hormones. Investigating the regulatory mechanisms behind osteoblast differentiation is important for bone regeneration therapy. miRNAs are known as important regulators, not only in a variety of cellular processes, but also in the pathogenesis of bone diseases. In the present study, we investigated the potential roles of miR-206 during osteoblast differentiation. We report that miR-206 expression was significantly down-regulated in human bone marrow mesenchymal stem cells (BMSCs) at days 7 and 14 during osteogenic induction. Furthermore, miR-206 overexpressing BMSCs showed attenuated alkaline phosphatase (ALP) activity, Alizarin Red staining, and osteocalcin secretion. The mRNA levels of osteogenic markers, Runx2 and Osteopontin (OPN), were significantly down-regulated in miR-206 overexpressing BMSCs. We observed that significantly increased glutamine uptake at days 7 and 14 during the osteogenic induction and inhibition of glutamine metabolism by knocking down glutaminase (GLS)-suppressed osteogenic differentiation of BMSCs. Here, we discover that miR-206 could directly bind to the 3′-UTR region of GLS mRNA, resulting in suppressed GLS expression and glutamine metabolism. Finally, restoration of GLS in miR-206 overexpressing BMSCs led to recovery of glutamine metabolism and osteogenic differentiation. In summary, these results reveal a new insight into the mechanisms of the miR-206-mediated osteogenesis through regulating glutamine metabolism. Our study may contribute to the development of therapeutic agents against bone diseases.

scholarly journals Mechanisms of Zuogui Pill in Treating Osteoporosis: Perspective from Bone Marrow Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Aofei Yang ◽  
Chaochao Yu ◽  
Fang You ◽  
Chengjian He ◽  
Zhanghua Li
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Metabolism ◽  
Scientific Evidence ◽  
Adipogenic Differentiation ◽  
Treatment Strategies ◽  
Marrow Mesenchymal Stem Cells ◽  
Zuogui Pill

The current treatment strategies for osteoporosis (OP) involve promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). According to a theory of traditional Chinese medicine (TCM), the kidneys contain an “essence” that regulate bone metabolism and generate marrow. Kidney disorders are therefore considered to be a major cause of OP as per the principles of TCM, which recommends kidney-tonifying treatments for OP. The Zuogui pill (ZGP) is a classic kidney-tonifying medication that effectively improves OP symptoms. Studies have shown that ZGP can promote the osteogenic differentiation of BMSCs, providing scientific evidence for the TCM theory linking kidneys with bone metabolism. In this review, we have provided an overview of recent studies that examined the underlying mechanisms of ZGP mediated regulation of BMSC osteogenic and adipogenic differentiation.

Tumor Necrosis Factor-α Inhibits Differentiation of Bone Marrow Mesenchymal Stem Cells into Osteoblasts by Inhibiting Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Pathway

2020 ◽  
Vol 10 (1) ◽  
pp. 127-132
Author(s):  
Teng Zhang ◽  
Guangjiang Ding ◽  
Wen Yang ◽  
Zhongyu Xiao
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Necrosis Factor ◽  
Osteogenic Differentiation ◽  
Real Time Pcr ◽  
Tumor Necrosis ◽  
Akt Pathway ◽  
Marrow Mesenchymal Stem Cells ◽  
Necrosis Factor

Bone marrow mesenchymal stem cells (BMSCs) have the potential for multi-directional differentiation. Tumor necrosis factor-α (TNF-α) plays a role in many diseases. However, the role of TNF-α in the differentiation of BMSCs into osteoblasts remains unclear. Rat-derived BMSCs were divided into normal control group and TNF-α group (5 ng/ml or 10 ng/ml) followed by analysis of BMSCs proliferation by MTT, Caspase3 activity, TNF-α mRNA and serum secretion by Real time PCR and ELISA, ALP activity, Runx2, OP and OC level by Real time PCR and PI3K/AKT signaling protein expression by Western blot. TNF-α significantly promoted the expression of TNF-α mRNA and serum secretion, inhibited cell proliferation, increased Caspase3 and ALP activity, decreased Runx2 and OP expression, and inhibited AKT phosphorylation compared to control (P < 0.05). The inhibition of osteogenic differentiation of BMSCs was more obvious with the increase of TNF-α concentration. TNF-α can inhibit the proliferation of BMSCs, promote apoptosis and inhibit BMSCs osteogenic differentiation via inhibiting the PI3K/AKT pathway.

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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