Ghrelin inhibits early osteogenic differentiation of C3H10T1/2 cells by suppressing Runx2 expression and enhancing PPARγ and C/EBPα expression

2009 ◽  
Vol 106 (4) ◽  
pp. 626-632 ◽  
Author(s):  
Sang Wan Kim ◽  
Ok Kyung Choi ◽  
Ju Yeon Jung ◽  
Jae-Yeon Yang ◽  
Sun Wook Cho ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Runx2 Expression

miRNA-126 Inhibits Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells (BMSCs)

2022 ◽  
Vol 12 (4) ◽  
pp. 794-799
Author(s):  
Le Chang ◽  
Wei Duan ◽  
Chuang Wang ◽  
Jian Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Mrna Level ◽  
Alizarin Red ◽  
Runx2 Expression ◽  
Alp Activity ◽  
Smad4 Protein ◽  
Marrow Mesenchymal Stem Cells

This study was to determine whether microRNA (miRNA)-126 regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Rat BMSCs were extracted and stimulated for osteogenic differentiation. Functional experiments were conducted to assess miR-126’s impact on BMSCs differentiation. Western blot and RT-qPCR determined miR-126 expression. ALP activity detection and alizarin red staining detection were also performed. After osteogenic differentiation of BMSCs, miR-126 expression was gradually decreased over time. Overexpression of miR-26 decreased ALP activity, Notch signaling activity as well as declined Runx2 expression and calcium Salt nodules after treatment. Importantly, we found that Smad4 serves as a target of miR-126 while upregulation of the miRNA was accompanied with the decreased Smad4 protein expression without affecting the Smad4 mRNA level. In conclusion, miR-126 restrains osteogenic differentiation through inhibition of SMAD4 signaling, providing a novel insight into the mechanism.

The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression

Bone ◽  
2010 ◽  
Vol 46 (6) ◽  
pp. 1498-1507 ◽  
Author(s):  
Su Jin Park ◽  
Seung-Hyun Jung ◽  
Gadi Jogeswar ◽  
Hyun-Mo Ryoo ◽  
Jong In Yook ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Osteogenic Differentiation ◽  
Runx2 Expression

Exosome-Derived miR21/SMAD7 Derived from Donor Osteoporosis Mesenchymal Stem Cells Inhibits Osteogenic Differentiation of Reconstituted Hosts

2019 ◽  
Vol 9 (10) ◽  
pp. 1346-1354
Author(s):  
Jie Chen ◽  
Yongsheng Luo ◽  
Ting Li ◽  
Wenbo Yang ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Runx2 Expression ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells ◽  
Smad7 Expression ◽  
Different Sources ◽  
Adult Mscs ◽  
Normal Adults

Exogenous bone marrow mesenchymal stem cells (MSCs) can regulate osteogenic differentiation. MicroRNA-21 has been shown to target SMAD7. This study explored the mechanism by which miR-21/SMAD7 inhibits osteogenic differentiation from exosomes secreted by osteoporosis patients-derived MSCs. Exosomes were obtained from MSCs and miR-21 expression was detected. Normal MSCs were treated with exosomes secreted by MSCs from different sources for osteogenic differentiation followed by detection of ALP, Bglap and Runx2 level and ALP activity. Normal MSCs were divided into three groups, which were treated with exosomes from normal adult MSCs, osteoporosis patients-derived MSCs and osteoporosis patients-derived MSCs + SMAD7 overexpression followed by analysis of the mRNA expression of ALP, Bglap and Runx2 by qRT-PCR and ALP activity. miR-21 expression in exosomes from osteoporosis patients-derived MSCs was significantly higher than that from normal adults MSCs. After treatment with exosomes from osteoporosis patients-derived MSCs, Runx2 expression and ALP activity was significantly decreased. SMAD7 expression in osteoporosis patients was significantly lower than that in normal adults. The expression of ALP, Bglap and Runx2 is significantly decreased after overexpression of SMAD7. SMAD7 is a target gene of miR-21 and plays a role in inhibiting osteogenic differentiation induced by exosomes from osteoporosis-derived MSCs.

Effect of Mir-1301 on the Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Hormone Osteonecrosis via Regulating SRY Related High Mobility Group Box 11 (SOX-11)

2020 ◽  
Vol 10 (12) ◽  
pp. 1858-1864
Author(s):  
Bingshen Jia ◽  
Guoxin Qu ◽  
Peng Yu ◽  
Tuo Jiao ◽  
ZiZhenbiao Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Osteogenic Differentiation ◽  
Real Time ◽  
Real Time Pcr ◽  
High Mobility ◽  
Hormone Treatment ◽  
Widespread Application ◽  
Runx2 Expression ◽  
Promote Cell Proliferation ◽  
Alp Activity

The widespread application of hormones leads to steroidal osteonecrosis and BMSCs have important roles in treating steroidal osteonecrosis. Mir-1301 involves in several diseases. However, Mir-1301’s effect on BMSCs proliferation and osteogenic differentiation in hormonal osteonecrosis has not been elucidated. Rat BMSCs were isolated and assigned into control groups; Dex group (1μM dexamethasone was added); Mir-1301 group and si-Mir-1301 group followed by analysis of miR-1301 and SOX11 level by Real time PCR, cell proliferation by MTT assay, Caspase3 activity kit, OPN and Runx2 expression by Real time PCR, and ALP activity. Under hormone treatment, Mir-1301 expression in BMSCs cells was significantly increased, proliferation was inhibited, Caspase3 activity was increased, SOX11, OPN and Runx2 expression was decreased and ALP activity was reduced (P <0.05). The above changes were more significant after transfection of Mir-1301 mimics (P <0.05). The addition of Mir-1301 inhibitor to Dex-treated BMSCs could down-regulate Mir-1301, significantly increase the expression of SOX11, OPN and Runx2, promote cell proliferation, decrease Caspase3 activity and increase ALP activity (P <0.05). The target gene of Mir-1301 is SOX11. Mir-1301 expression in BMSCs cells is increased during steroid-induced osteonecrosis. Down-regulating Mir-1301 during steroid-induced osteonecrosis can inhibit BMSCs apoptosis and promote proliferation and osteogenesis via targeting SOX11.

Osteogenic differentiation of human gingival mesenchymal stem cells byAristolochia bracteolatasupplementation through enhanced Runx2 expression

2017 ◽  
Vol 232 (7) ◽  
pp. 1591-1595 ◽  
Author(s):  
Dinesh Murugan Girija ◽  
Suresh Y Ranga Rao ◽  
Mangathayaru Kalachaveedu ◽  
Rajasekaran Subbarayan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Runx2 Expression

scholarly journals HDAC6 inactivates Runx2 promoter to block osteogenesis of bone marrow stromal cells in age-related bone loss of mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chao Ma ◽  
Juan Gao ◽  
Jun Liang ◽  
Weixiang Dai ◽  
Zhenfei Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Differentiation Potential ◽  
Runx2 Expression ◽  
Aged Mice ◽  
Age Related ◽  
Old Mice

Abstract Background Senile osteoporosis can cause bone fragility and increased risk for fractures and has been one of the most prevalent and severe diseases affecting the elderly population worldwidely. The underlying mechanisms are currently intensive areas of investigation. In age-related bone loss, decreased bone formation overweighs increased bone resorption. The molecular mechanisms underlying defective bone formation in age-related bone loss are not completely understood. In particular, the specific role of histone acetylation in age-related bone loss has not been examined thoroughly. Methods We employed 6- and 18-month-old mice to investigate the mechanisms of defective bone formation in age-related bone loss. Bone marrow stromal cells (BMSCs) were induced to undergo in vitro osteogenic differentiation. Chromatin immunoprecipitation (ChIP) was used to investigate the binding of histone deacetylases (HDACs) on Runx2 promoter in BMSCs. Luciferase reporter and transient transfection assay were employed to study Runx2 gene expression modulation by HDAC and androgen receptor (AR). siRNA and HDAC6 inhibitor, Tubastatin A, were used to inhibit HDAC6 in vitro. And systemic administration of Tubastatin A was used to block HDAC6 in vivo. Results Age-related trabecular bone loss was observed in 18-month-old mice compared with 6-month-old mice. In vitro osteogenic differentiation potential of BMSCs from 18-month-old mice was weaker than 6-month-old mice, in which there was Runx2 expression inactivation in BMSCs of 18-month-old mice compared with 6-month-old mice, which was attributable to HDAC6-mediated histone hypoacetylation in Runx2 promoter. There was competitive binding of HDAC6 and AR on Runx2 promoter to modulate Runx2 expression in BMSCs. More importantly, through siRNA- or specific inhibitor-mediated HDAC6 inhibition, we could activate Runx2 expression, rescue in vitro osteogenesis potential of BMSCs, and alleviate in vivo age-related bone loss of mice. Conclusion HDAC6 accumulation and histone hypoacetylation on Runx2 promoter contributed to the attenuation of in vitro osteogenic differentiation potential of BMSCs from aged mice. Through HDAC6 inhibition, we could activate Runx2 expression and osteogenic differentiation potential of BMSCs from aged mice and alleviate the age-related bone loss of aged mice. Our study will benefit not only for understanding the age-related bone loss, but also for finding new therapies to treat senile osteoporosis.

scholarly journals Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA MALAT1 May Partially Contribute to Randall’s Plaque Formation

2021 ◽  
Vol 8 ◽  
Author(s):  
Zewu Zhu ◽  
Fang Huang ◽  
Weiping Xia ◽  
Huimin Zeng ◽  
Meng Gao ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Transcription Initiation ◽  
Potential Role ◽  
Ectopic Calcification ◽  
Competing Endogenous Rna ◽  
Runx2 Expression ◽  
Lncrna Malat1 ◽  
Current Belief ◽  
Rna Immunoprecipitation ◽  
Randall’S Plaques

BackgroundThe current belief is that Randall’s plaques (RP) constitute a nidus for the formation of idiopathic calcium oxalate stones, but the upstream events in RP formation remain unclear. The present study aimed to investigate whether RP formation shares similarities with biomineralization and to illustrate the potential role played by the lncRNA MALAT1 in osteogenic differentiation of human renal interstitial fibroblasts (hRIFs).Materials and MethodsBiomineralization and MALAT1 expression were assessed in RP, and hRIFs were isolated and induced under osteogenic conditions for further experiments. The transcription initiation and termination sites in MALAT1 were identified by 5′ and 3′ RACE. RNA immunoprecipitation assays and luciferase assays were used to validate the interactions among MALAT1, Runx2 and miRNAs.ResultsUpregulated expression of osteogenic markers and MALAT1 was observed in RP and hRIFs induced with osteogenic medium. Biomineralization in RP and calcium phosphate (CaP) deposits in induced hRIFs were further verified by electron microscopy. Furthermore, overexpression of MALAT1 promoted the osteogenic phenotype of hRIFs, while treatment with a miR-320a-5p mimic and knockdown of Runx2 significantly suppressed the osteogenic phenotype. Further analysis showed that MALAT1 functioned as a competing endogenous RNA to sponge miR-320a-5p, leading to upregulation of Runx2 and thus promoting osteogenic differentiation of hRIFs.ConclusionEctopic calcification and MALAT1 partially contributed to the formation of RP, in which MALAT1 might promote Runx2 expression to regulate osteogenic differentiation of hRIFs by sponging miRNA-320a-5p. The current study sheds new light on the lncRNA-directed mechanism of RP formation via a process driven by osteogenic-like cells.

scholarly journals c-Src kinase inhibits osteogenic differentiation via enhancing STAT1 stability

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241646
Author(s):  
Zahra Alvandi ◽  
Michal Opas
Keyword(s):  
Osteogenic Differentiation ◽  
Transcriptional Activity ◽  
Embryonic Stem ◽  
Detectable Effect ◽  
Runx2 Expression ◽  
Inhibitory Role ◽  
Molecule Inhibitor ◽  
Related Transcription Factor

The proto-oncogene Src is ubiquitously expressed and is involved in cellular differentiation. However, the role of Src in embryonic stem (ES) cell osteogenic differentiation is largely unknown. Using the small molecule inhibitor PP2, c-Src specific siRNAs, and tet-inducible lentiviral vectors overexpressing active c-Src, we delineated an inhibitory role of c-Src in osteogenic differentiation of mouse embryonic stem cells (mESCs) and mouse MC3T3-E1s preosteoblasts. Active c-Src was shown to restrict the nuclear residency of Runt-related transcription factor 2 (Runx2) and its transcriptional activity with no detectable effect on Runx2 expression level. Furthermore, we showed Signal Transducer and Activator of Transcription 1 (STAT1) was indispensable to the inhibitory role of c-Src on Runx2 nuclear localization. Specifically, higher levels of active c-Src increased STAT1 half-life by inhibiting its proteasomal degradation, thereby increasing the cytoplasmic abundance of STAT1. More abundant cytoplasmic STAT1 bound and anchored Runx2, which restricted its nucleocytoplasmic shuttling and ultimately reduced Runx2 transcriptional activity. Collectively, this study has defined a new mechanism by which c-Src inhibits the transcriptional regulation of osteogenesis from mESCs in vitro.

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