scholarly journals Let-7c regulates proliferation and osteodifferentiation of human adipose-derived mesenchymal stem cells under oxidative stress by targeting SCD-1

2019 ◽  
Vol 316 (1) ◽  
pp. C57-C69 ◽  
Author(s):  
Zihui Zhou ◽  
Yuanshan Lu ◽  
Yao Wang ◽  
Lin Du ◽  
Yunpeng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Postmenopausal Osteoporosis ◽  
Luciferase Reporter ◽  
Matrix Mineralization ◽  
Protein Levels ◽  
Micro Rnas

Osteoporosis is a progressive bone disease characterized by decreased bone mass and density, which usually parallels a reduced antioxidative capacity and increased reactive oxygen species formation. Adipose-derived mesenchymal stem cells (ADMSCs), a population of self-renewing multipotent cells, are a well-recognized source of potential bone precursors with significant clinical potential for tissue regeneration. We previously showed that overexpressing stearoyl-CoA desaturase 1 (SCD-1) promotes osteogenic differentiation of mesenchymal stem cells. Micro-RNAs (miRNAs) are noncoding RNAs recently recognized to play key roles in many developmental processes, and miRNA let-7c is downregulated during osteoinduction. We found that let-7c was upregulated in the serum of patients with postmenopausal osteoporosis compared with healthy controls. Levels of let-7c during osteogenic differentiation of ADMSCs were examined under oxidative stress in vitro and found to be upregulated. Overexpression of let-7c inhibited osteogenic differentiation, whereas inhibition of let-7c function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase activity, and matrix mineralization. The luciferase reporter assay was used to validate SCD-1 as a target of let-7c. Further experiments showed that silencing of SCD-1 significantly attenuated the effect of let-7c inhibitor on osteoblast markers, providing strong evidence that let-7c modulates osteogenic differentiation by targeting SCD-1. Inhibition of let-7c promoted the translocation of β-catenin into nuclei, thus activating Wnt/β-catenin signaling. Collectively, these data suggest that let-7c is induced under oxidative stress conditions and in osteoporosis, reducing SCD-1 protein levels, switching off Wnt/β-catenin signaling, and inhibiting osteogenic differentiation. Thus, let-7c may be a potential therapeutic target in the treatment of osteoporosis and especially postmenopausal osteoporosis.

scholarly journals MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

2016 ◽  
Vol 38 (2) ◽  
pp. 809-820 ◽  
Author(s):  
Lei Yang ◽  
Dawei Ge ◽  
Xiaojian Cao ◽  
Yingbin Ge ◽  
Hongtao Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Postmenopausal Osteoporosis ◽  
Osteoblast Differentiation ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Matrix Mineralization ◽  
Direct Target

Background/Aims: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. Methods: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. Results: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. Conclusions: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.

scholarly journals MicroRNA-346-5p Regulates Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells by Inhibiting Transmembrane Protein 9

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yicai Zhang ◽  
Yi Sun ◽  
Jinlong Liu ◽  
Yu Han ◽  
Jinglong Yan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Protein Level ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Luciferase Reporter ◽  
Alizarin Red ◽  
Protein Levels

The molecular mechanisms how bone marrow-derived mesenchymal stem cells (BMSCs) differentiate into osteoblast need to be investigated. MicroRNAs (miRNAs) contribute to the osteogenic differentiation of BMSCs. However, the effect of miR-346-5p on osteogenic differentiation of BMSCs is not clear. This study is aimed at elucidating the underlying mechanism by which miR-346-5p regulates osteogenic differentiation of human BMSCs. Results of alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining indicated that upregulation of miR-346-5p suppressed osteogenic differentiation of BMSCs, whereas downregulation of miR-346-5p enhanced this process. The protein levels of the osteoblastic markers Osterix and Runt-related transcription factor 2 (Runx2) were decreased in cells treated with miR-346-5p mimic at day 7 and day 14 after being differentiated. By contrast, downregulation of miR-346-5p elevated the protein levels of Osterix and Runx2. Moreover, a dual-luciferase reporter assay revealed that Transmembrane Protein 9 (TMEM9) was a target of miR-346-5p. In addition, the Western Blot results demonstrated that the TMEM9 protein level was significantly reduced by the miR-346-5p mimic whereas downregulation of miR-346-5p improved the protein level of TMEM9. These results together demonstrated that miR-346-5p served a key role in BMSC osteogenic differentiation of through targeting TMEM9, which may provide a novel target for clinical treatments of bone injury.

Impaired Osteogenic Differentiation of Mesenchymal Stem Cells Derived From Multiple Myeloma Patients Is Associated with a Failure In the Deactivation of the NOTCH Pathway

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1894-1894
Author(s):  
Song Xu ◽  
Jinsong Hu ◽  
Dehui Xu ◽  
Isabelle Vande Broek ◽  
Xavier Leleu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Notch Pathway ◽  
Notch Signalling ◽  
Matrix Mineralization ◽  
Alp Activity ◽  
Hes1 Expression

Abstract Abstract 1894 Mesenchymal stem cells (MSCs) give rise to bone marrow (BM) stromal cells and play an essential role in the formation and function of the MM microenvironment. Some recent studies revealed that MSCs from myeloma patients (MM-hMSCs) show an enhanced spontaneous and myeloma cell-induced production of cytokines and a distinctive gene expression profile, when compared to MSCs from normal donors (ND-hMSCs). However, regarding the osteogenic differentiation ability of MM-hMSCs conflicting observations were reported. In this study, we observed that MM-hMSCs, especially for those from MM patients with bone lesions, exhibited in the presence of osteogenic differentiation (OD) medium, significantly decreased alkaline phosphatase (ALP) activity, reduced expression of specific osteogenic markers (OPN, BMP2, OTX and BSP) and impaired matrix mineralization, compared to ND-hMSCs. However, MGUS-hMSCs, did not show a significantly impaired osteogenesis ability. Primary CFU-ALP assay from BM samples of diseased mice in the 5T33MM model also confirmed that the osteogenic differentiation ability of MSCs was impaired. Previous reports indicated that MM cells can suppress MSCs osteogenesis by HGF and DKK1 as observed in vitro (Giuliani et al, Cancer Res. 2007; Standal et al, Blood. 2007). Since MM-hMSCs have been cultured in vitro for several weeks and without any stimulation of MM cells, we believe that the impaired osteogenic differentiation of MM-hMSCs was due to an intrinsic abnormality. Several reports suggested that NOTCH signalling can maintain bone marrow mesenchymal progenitors in a more undifferentiated state by suppressing osteoblast differentiation (Hilton et al, Nat Med. 2008; Zanotti et al, Endocrinology. 2008). Therefore, we postulate that impaired osteogenic ability of MM-hMSCs might be (at least partly) related to abnormal NOTCH activity during osteogenesis. We found by quantitative real time PCR that NOTCH1, NOTCH2, Dll-1, Jagged-1, and NOTCH pathway downstream genes hes1, hey1, hey2, heyL were considerably decreased in ND-hMSCs after shifting them from normal culture medium to OD medium, indicating that NOTCH signalling was gradually suppressed during MSC osteogenesis. However, it was observed that the expression of NOTCH1, Jagged-1, Hes1 and Hes5 in MM-hMSCs did not decrease to the level of ND-hMSC with statistical difference. This implicates that the NOTCH signaling pathway remains in MM-hMSCs over-activated even in the presence of osteogenesis inducing signals. When the NOTCH signalling inhibitor DAPT was added to MM-hMSCs in OD medium, we found that hes1 expression was suppressed while, RUNX2 expression, a key transcription factor for osteoblastogenesis, as well as ALP activity, osteogenic genes expression and mineralization deposition were all increased. In conclusion our data indicate that MM-hMSCs exhibit in vitro lower osteogenic differentiation ability compared to ND-hMSCs, and that this impairement is associated with an inappropriate NOTCH pathway deactivation during the osteogenesis process. Targeting hMSCs in vivo by NOTCH inhibitors might have therapeutical potential to control bone disease in MM patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Resveratrol Induces the Osteogenic Differentiation via MiR-320c by Targeting Runx2 and Is Involved in the Adipogenic differentiation of BMSCs

2020 ◽  
Author(s):  
Jilong Zou ◽  
Jianyang Du ◽  
Hualei Tu ◽  
Hongjun Chen ◽  
Kai Cong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Target Gene ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Matrix Mineralization

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are multipotent progenitor cells and have been widely used in clinical therapies due to their multiple pluripotency. Recent publications have found that resveratrol (RSVL) could promote the proliferation and differentiation of mesenchymal stem cells; however, the underlying molecular mechanism of RSVL-induced BMSCs osteogenic differentiation needs to be fully elucidated. The aim of this study was to investigate the function of miRNAs in RSVL-treated BMSCs and its effects on the osteogenic differentiation of BMSCs. Methods BMSCs were cultured and treated with different concentrations of RSVL. After osteogenic differentiation for 20 days, ALP staining was performed to evaluate the ALP activity of BMSCs. And ARS staining was used to detect the matrix mineralization deposition of BMSCs. After adipogenic differentiation for 20 days, adipogenic differentiation was determined by ORO staining for lipid droplets. Quantitative real-time polymerase chain reaction analysis was performed to assess the expression level of target genes. Bioinformatics analysis and luciferase reporter assay was ultilized to examine the relationship between miR-320c and its target gene. Western blot assay was used to analyze the protein expression level of target gene. Results Our results demonstrated that RSVL could promote the osteogenic differentiation and suppressed the adipogenic differentiation of BMSCs in a dose-dependent manner. Besides, a novel regulatory axis containing miR-320c and its target Runx2 was found during the differentiation process of BMSCs under RSVL treatment. Overexpression of miR-320c inhibited the osteogenic differentiation, while knockdown of miR-320c promoted the osteogenic differentiation of BMSCs. In contrast, overexpression of miR-320c accelerated the adipogenic differentiation, while knockdown of miR-320c restrained the adipogenic differentiation of BMSCs. Our results confirm that Runx2 was the directly target of miR-320c in RSVL-promoted osteogenic differentiation of BMSCs. Conclusions The present study revealed that miR-320c might possess the potentials as a novel clinical target for medical intervention to regulate the biological functions of RSVL in BMSCs.

scholarly journals The role of Serpina3n in the reversal effect of ATRA on dexamethasone-inhibited osteogenic differentiation in mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hai-Tao Jiang ◽  
Rui Deng ◽  
Yan Deng ◽  
Mao Nie ◽  
Yi-Xuan Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Chip Assay ◽  
Rna Seq ◽  
Matrix Mineralization ◽  
Reversal Effect ◽  
Osteogenic Markers

Abstract Background Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Patients with GIOP are susceptible to fractures and the subsequent delayed bone union or nonunion. Thus, effective drugs and targets need to be explored. In this regard, the present study aims to reveal the possible mechanism of the anti-GIOP effect of all-trans retinoic acid (ATRA). Methods Bone morphogenetic protein 9 (BMP9)-transfected mesenchymal stem cells (MSCs) were used as an in vitro osteogenic model to deduce the relationship between ATRA and dexamethasone (DEX). The osteogenic markers runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin were detected using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescent staining assay. ALP activities and matrix mineralization were evaluated using ALP staining and Alizarin Red S staining assay, respectively. The novel genes associated with ATRA and DEX were detected using RNA sequencing (RNA-seq). The binding of the protein–DNA complex was validated using chromatin immunoprecipitation (ChIP) assay. Rat GIOP models were constructed using intraperitoneal injection of dexamethasone at a dose of 1 mg/kg, while ATRA intragastric administration was applied to prevent and treat GIOP. These effects were evaluated based on the serum detection of the osteogenic markers osteocalcin and tartrate-resistant acid phosphatase 5b, histological staining, and micro-computed tomography analysis. Results ATRA enhanced BMP9-induced ALP, RUNX2 expressions, ALP activities, and matrix mineralization in mouse embryonic fibroblasts as well as C3H10T1/2 and C2C12 cells, while a high concentration of DEX attenuated these markers. When DEX was combined with ATRA, the latter reversed DEX-inhibited ALP activities and osteogenic markers. In vivo analysis showed that ATRA reversed DEX-inhibited bone volume, bone trabecular number, and thickness. During the reversal process of ATRA, the expression of retinoic acid receptor beta (RARβ) was elevated. RARβ inhibitor Le135 partly blocked the reversal effect of ATRA. Meanwhile, RNA-seq demonstrated that serine protease inhibitor, clade A, member 3N (Serpina3n) was remarkably upregulated by DEX but downregulated when combined with ATRA. Overexpression of Serpina3n attenuated ATRA-promoted osteogenic differentiation, whereas knockdown of Serpina3n blocked DEX-inhibited osteogenic differentiation. Furthermore, ChIP assay revealed that RARβ can regulate the expression of Serpina3n. Conclusion ATRA can reverse DEX-inhibited osteogenic differentiation both in vitro and in vivo, which may be closely related to the downregulation of DEX-promoted Serpina3n. Hence, ATRA may be viewed as a novel therapeutic agent, and Serpina3n may act as a new target for GIOP.

scholarly journals miR-125a-5p Regulates Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells under Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yongheng Ye ◽  
Quan Liu ◽  
Changzhao Li ◽  
Peiheng He
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Tissue Regeneration ◽  
Negative Group ◽  
Related Transcription Factor ◽  
Bone Repairing

Adipose-derived mesenchymal stem cells (ADSCs) are a well-recognized multilineage stem cell with vital clinical feasibility for tissue regeneration. Extensive evidence indicates that oxidative stress and microRNAs (miRNAs/miRs) play an important role in the osteoinduction of adipose-derived mesenchymal stem cells. In this study, we investigated the mechanism of miR-125a-5p in regulating the osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) under oxidative stress. The expression of miR-125a-5p lessened gradually during the osteogenic differentiation of hADSCs. Relative to the negative group, the expression levels of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osterix in the miR-125a-5p group were marked lower than those in the miR-125a-5p inhibitor group. The levels of p16, p21, p53, miR-125a-5p, and ROS during osteoinduction of hADSCs were assessed in vitro under oxidative stress and were observed to be upregulated. Further experiments showed that oxidative stress and miR-125a-5p together suppressed the expression of VEGF during osteogenic differentiation of hADSCs and that the inhibition of miR-125a-5p reversed the effect of oxidative stress. In short, our study indicated that miR-125a-5p is induced under oxidative stress and inhibits the expression of VEGF, leading to the reduction of osteogenic differentiation of hADSCs. Our outcomes showed that miR-125a-5p could be a potential clinical target for bone repairing.

scholarly journals Applying vibration in early postmenopausal osteoporosis promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells and suppresses postmenopausal osteoporosis progression

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Huiming Li ◽  
Wenchao Wu ◽  
Xueling He ◽  
Chengjian Cao ◽  
Xiaoqin Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Postmenopausal Osteoporosis ◽  
Biomechanical Properties ◽  
Estradiol Benzoate ◽  
Once Daily ◽  
Underlying Mechanisms

Abstract We aimed to evaluate whether applying low magnitude vibration (LMV) in early postmenopausal osteoporosis (PMO) suppresses its progression, and to investigate underlying mechanisms. Rats were randomly divided into Sham (Sham-operated), Sham+V, OVX (ovariectomized), OVX+E2 (estradiol benzoate), OVX+V (LMV at 12–20 weeks postoperatively), and OVX+Vi (LMV at 1–20 weeks postoperatively) groups. LMV was applied for 20 min once daily for 5 days weekly. V rats were loaded with LMV at 12–20 weeks postoperatively. Vi rats were loaded with LMV at 1–20 weeks postoperatively. Estradiol (E2) rats were intramuscularly injected at 12–20 weeks postoperatively once daily for 3 days. The bone mineral densities (BMDs), biomechanical properties, and histomorphological parameters of tibiae were analyzed. In vitro, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were subjected to LMV for 30 min daily for 5 days, or 17β-E2 with or without 1-day pretreatment of estrogen receptor (ER) inhibitor ICI 182,780 (ICI). The mRNA and protein expresion were performed. Data showed that LMV increased BMD, bone strength, and bone mass of rats, and the effects of Vi were stronger than those of E2. In vitro, LMV up-regulated the mRNA and protein expressions of Runx2, Osx, Col I, and OCN and down-regulated PPARγ, compared with E2. The effects of both LMV and E2 on rBMSCs were inhibited by ICI. Altogether, LMV in early PMO suppresses its progression, which is associated with osteogenic differentiation of rBMSCs via up-regulation of ERα and activation of the canonical Wnt pathway. LMV may therefore be superior to E2 for the suppression of PMO progression.

scholarly journals Systems biology analysis of osteogenic differentiation behavior by canine mesenchymal stem cells derived from bone marrow and dental pulp

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sirirat Nantavisai ◽  
Trairak Pisitkun ◽  
Thanaphum Osathanon ◽  
Prasit Pavasant ◽  
Chanin Kalpravidh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Systems Biology ◽  
Osteogenic Differentiation ◽  
Dental Pulp ◽  
Bmp Signaling ◽  
Functional Assay ◽  
Matrix Mineralization

AbstractUtilization of canine mesenchymal stem cells (cMSCs) for regenerating incorrigible bone diseases has been introduced. However, cMSCs harvested from different sources showed distinct osteogenicity. To clarify this, comparative proteomics-based systems biology analysis was used to analyze osteogenic differentiation behavior by cMSCs harvested from bone marrow and dental pulp. The results illustrated that canine dental pulp stem cells (cDPSCs) contained superior osteogenicity comparing with canine bone marrow-derived MSCs (cBM-MSCs) regarding alkaline phosphatase activity, matrix mineralization, and osteogenic marker expression. Global analyses by proteomics platform showed distinct protein clustering and expression pattern upon an in vitro osteogenic induction between them. Database annotation using Reactome and DAVID revealed contrast and unique expression profile of osteogenesis-related proteins, particularly on signaling pathways, cellular components and processes, and cellular metabolisms. Functional assay and hierarchical clustering for tracking protein dynamic change confirmed that cBM-MSCs required the presences of Wnt, transforming growth factor (TGF)-beta, and bone-morphogenetic protein (BMP) signaling, while cDPSCs mainly relied on BMP signaling presentation during osteogenic differentiation in vitro. Therefore, these findings illustrated the comprehensive data regarding an in vitro osteogenic differentiation behavior by cBM-MSCs and cDPSCs which is crucial for further mechanism study and the establishment of cMSC-based bone tissue engineering (BTE) for veterinary practice.

scholarly journals The Inhibitory Role of Di-2-ethylhexyl Phthalate on Osteogenic Differentiation of Mesenchymal Stem Cells Via Down-regulation of RUNX2 and Membrane Function Impairment

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Mohammad Hossein Abnosi ◽  
Zahra Aliyari Babolghani
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Lactate Dehydrogenase ◽  
Osteogenic Differentiation ◽  
Potassium Level ◽  
Down Regulation ◽  
Matrix Mineralization ◽  
Matrix Deposition

Background: Blood contamination of di-2-ethyl hexyl phthalate (DEHP) has been reported due to its release following medical procedures such as blood transfusion and vital liquid injection. We investigated the effect of DEHP on osteogenic differentiation of mesenchymal stem cells and their viability. Methods: The rat bone marrow mesenchymal cells (MSCs) were cultured three times, and the third passage kept in the differentiation medium with the presence of DEHP. The viability of differentiated cells, sodium and potassium level, calcium concentration, total protein concentration, and the activity of lactate dehydrogenase, alkaline phosphatase, alanine transaminase, and aspartate transaminase were determined. Also, the concentration of malondialdehyde, total antioxidant capacity, the activity of superoxide dismutase and catalase were estimated. Finally, the level of matrix deposition and expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX2) genes were evaluated.Results: We observed a concentration-dependent and significant reduction of matrix mineralization based on alizarin red and calcium analysis. Besides, the expression of ALP and RUNX2 gene was down-regulated, and alkaline-phosphatase activity reduced significantly. Also, we observed cell viability reduction but the elevation of lactate dehydrogenase activity and malondialdehyde level. Sodium level was elevated too, whereas the activity of transaminases, oxidative stress enzymes, potassium level, and total antioxidants decreased. Conclusion: DEHP contamination reduced matrix mineralization due to the down-regulation of the genes involved in osteogenic differentiation and viability reduction via electrolyte and metabolic imbalance as well as induction of oxidative stress.

scholarly journals MiR-128 promotes osteogenic differentiation of bone marrow mesenchymal stem cells in rat by targeting DKK2

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Can Wang ◽  
Xianghe Qiao ◽  
Zhuang Zhang ◽  
Chunjie Li
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Bone Growth ◽  
Wnt Signaling Pathway ◽  
Osteoblastic Differentiation ◽  
Matrix Mineralization ◽  
Protein Levels ◽  
Marrow Mesenchymal Stem Cells

Abstract Bone loss caused by inflammatory disease, such as peri-implantitis, poses a great challenge to clinicians for restoration. Emerging evidence indicates that microRNAs (miRNAs) are indispensable regulators of bone growth, development, and formation. In the present study, we found that microRNA-128 (miR-128) was differentially up-regulated during the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Overexpression of miR-128 promoted osteogenic differentiation of rBMSCs by up-regulating alkaline phosphatase (ALP), matrix mineralization, mRNA, and protein levels of osteogenic makers (e.g. RUNX2, BMP-2, and COLIA1), whereas inhibition of miR-128 suppressed osteoblastic differentiation in vitro. Mechanistically, miR-128 directly and functionally targeted Dickkopf2 (DKK2), which is a Wnt signaling pathway antagonist, and enhanced Wnt/β-catenin signaling activity. Furthermore, the positive effect of miR-128 on osteogenic differentiation was apparently abrogated by DKK2 overexpression. Collectively, these results indicate that miR-128 promotes osteogenic differentiation of rBMSCs by targeting DKK2, which may provide a promising approach to the treatment of peri-implantitis.

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