scholarly journals N-Acetyl-l-leucine-polyethylenimine-mediated miR-34a delivery improves osteogenesis and bone formationin vitroandin vivo

RSC Advances ◽  
2018 ◽  
Vol 8 (15) ◽  
pp. 8080-8088 ◽  
Author(s):  
Yuqin Shen ◽  
Yin Liu ◽  
Han Gao ◽  
Hongbo Fei ◽  
Wenwen Yu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Transfection Efficiency

We employN-acetyl-l-leucine-modified polyethylenimine as an miR-34a carrier and evaluate its delivery ability, transfection efficiency, cytotoxicity and whether it enhances osteogenic differentiation and bone formationin vitroandin vivo.

scholarly journals ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dan Zhang ◽  
Kim De Veirman ◽  
Rong Fan ◽  
Qiang Jian ◽  
Yuchen Zhang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Er Stress ◽  
Osteogenic Differentiation ◽  
Osteoblast Differentiation ◽  
Bone Destruction ◽  
Proteasome Inhibition ◽  
Stress Signaling ◽  
Alizarin Red

Abstract Background Bone destruction is a hallmark of multiple myeloma (MM). It has been reported that proteasome inhibitors (PIs) can reduce bone resorption and increase bone formation in MM patients, but the underlying mechanisms remain unclear. Methods Mesenchymal stem cells (MSCs) were treated with various doses of PIs, and the effects of bortezomib or carfilzomib on endoplasmic reticulum (ER) stress signaling pathways were analyzed by western blotting and real-time PCR. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to determine the osteogenic differentiation in vitro. Specific inhibitors targeting different ER stress signaling and a Tet-on inducible overexpressing system were used to validate the roles of key ER stress components in regulating osteogenic differentiation of MSCs. Chromatin immunoprecipitation (ChIP) assay was used to evaluate transcription factor-promoter interaction. MicroCT was applied to measure the microarchitecture of bone in model mice in vivo. Results We found that both PERK-ATF4 and IRE1α-XBP1s ER stress branches are activated during PI-induced osteogenic differentiation. Inhibition of ATF4 or XBP1s signaling can significantly impair PI-induced osteogenic differentiation. Furthermore, we demonstrated that XBP1s can transcriptionally upregulate ATF4 expression and overexpressing XBP1s can induce the expression of ATF4 and other osteogenic differentiation-related genes and therefore drive osteoblast differentiation. MicroCT analysis further demonstrated that inhibition of XBP1s can strikingly abolish bortezomib-induced bone formation in mouse. Conclusions These results demonstrated that XBP1s is a master regulator of PI-induced osteoblast differentiation. Activation of IRE1α-XBP1s ER stress signaling can promote osteogenesis, thus providing a novel strategy for the treatment of myeloma bone disease.

scholarly journals Extracorporeal Shock Wave Therapy Promotes Osteogenic Differentiation in a Rabbit Osteoporosis Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Baofeng Li ◽  
Renkai Wang ◽  
Xianyin Huang ◽  
Yongliang Ou ◽  
Zhenyu Jia ◽  
...  
Keyword(s):  
Shock Wave ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Detailed Mechanism ◽  
Extracorporeal Shock Wave ◽  
Osteoblast Maturation

Extracorporeal shock wave therapy (ESWT) has been identified to accelerate bone formation. However, detailed mechanism has not been fully explained. In this study, we found that ESWT promoted osteoblast formation in vitro. Local ESW treatment of femur increased bone formation in vivo. Furthermore, changing the density or frequency of energy, there was no statistical difference in osteogenic differentiation. Therapeutically, local ESW therapy relieved bone loss and increased the number of bone trabecular in a rabbit osteoporosis model and promoted endogenous levels of SMAD2 protein expression. Thus, ESWT may be a potential therapy by promoting osteoblast maturation through TGF-β/SMAD2 pathway.

miR-450b Promotes Osteogenic Differentiation In Vitro and Enhances Bone Formation In Vivo by Targeting BMP3

2018 ◽  
Vol 27 (9) ◽  
pp. 600-611 ◽  
Author(s):  
Linyuan Fan ◽  
Junfen Fan ◽  
Yan Liu ◽  
Tangping Li ◽  
Haoying Xu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Osteogenic Differentiation

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.

Strontium folic acid derivative functionalized titanium surfaces for enhanced osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo

2017 ◽  
Vol 5 (33) ◽  
pp. 6811-6826 ◽  
Author(s):  
Kui Xu ◽  
Weizhen Chen ◽  
Caiyun Mu ◽  
Yonglin Yu ◽  
Kaiyong Cai
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Folic Acid ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Acid Derivative ◽  
Titanium Surfaces

Strontium folic acid derivative (FASr) functionalized titanium surfaces improve the in vitro osteogenic differentiation of MSCs and osseointegration in vivo.

scholarly journals Effect of the HDAC inhibitor vorinostat on the osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo

2013 ◽  
Vol 34 (5) ◽  
pp. 699-709 ◽  
Author(s):  
Song Xu ◽  
Kim De Veirman ◽  
Holly Evans ◽  
Gaia Cecilia Santini ◽  
Isabelle Vande Broek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Hdac Inhibitor

scholarly journals The impact of Zn-doped synthetic polymer materials on bone regeneration: a systematic review

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Siyi Wang ◽  
Rong Li ◽  
Dandan Xia ◽  
Xiao Zhao ◽  
Yuan Zhu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Synthetic Polymers ◽  
Synthetic Polymer ◽  
Polymer Materials ◽  
In Vivo Experiments

Abstract Introduction To repair bone defects, a variety of bone substitution materials have been used, such as ceramics, metals, natural and synthetic polymers, and combinations thereof. In recent decades, a wide range of synthetic polymers have been used for bone regeneration. These polymers have the advantages of biocompatibility, biodegradability, good mechanical properties, low toxicity, and ease of processing. However, when used alone, they are unable to achieve ideal bone formation. Incorporating zinc (Zn) into synthetic polymers has been considered, as previous studies have shown that Zn2+ promotes stem cell osteogenesis and mineral deposition. The purpose of this systematic review was to provide an overview of the application and effectiveness of Zn in synthetic polymers for bone regeneration, whether used alone or in combination with other biomaterials. This study was performed according to the PRISMA guidelines. Materials and methods A search of the PubMed, Embase, and the Cochrane Library databases for articles published up to June 2020 revealed 153 relevant studies. After screening the titles, abstracts, and full texts, 13 articles were included in the review; 9 of these were in vitro, 3 were in vivo, and 1 included both in vitro and in vivo experiments. Results At low concentrations, Zn2+ promoted cell proliferation and osteogenic differentiation, while high-dose Zn2+ resulted in cytotoxicity and inhibition of osteogenic differentiation. Additionally, one study showed that Zn2+ reduced apatite formation in simulated body fluid. In all of the in vivo experiments, Zn-containing materials enhanced bone formation. Conclusions At appropriate concentrations, Zn-doped synthetic polymer materials are better able to promote bone regeneration than materials without Zn.

scholarly journals CGRP Regulates the Age-Related Switch Between Osteoblast and Adipocyte Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Hang Li ◽  
Jian Qu ◽  
Haihong Zhu ◽  
Jiaojiao Wang ◽  
Hao He ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Differentiation Potential ◽  
Aged Mice ◽  
Age Related ◽  
Calcitonin Gene

Osteoporosis is a chronic age-related disease. During aging, bone marrow-derived mesenchymal stem cells (BMSCs) display increased adipogenic, along with decreased osteogenic, differentiation capacity. The aim of the present study was to investigate the effect of calcitonin gene-related peptide (CGRP) on the osteogenic and adipogenic differentiation potential of BMSC-derived osteoblasts. Here, we found that the level of CGRP was markedly lower in bone marrow supernatant from aged mice compared with that in young mice. In vitro experiments indicated that CGRP promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation. Compared with vehicle-treated controls, aged mice treated with CGRP showed a substantial promotion of bone formation and a reduction in fat accumulation in the bone marrow. Similarly, we found that CGRP could significantly enhance bone formation in ovariectomized (OVX) mice in vivo. Together, our results suggested that CGRP may be a key regulator of the age-related switch between osteogenesis and adipogenesis in BMSCs and may represent a potential therapeutic strategy for the treatment of age-related bone loss.

scholarly journals The MicroRNA-23a Has Limited Roles in Bone Formation and Homeostasis In Vivo

2015 ◽  
pp. 711-719 ◽  
Author(s):  
J. PARK ◽  
S. WADA ◽  
T. USHIDA ◽  
T. AKIMOTO
Keyword(s):  
Transcription Factor ◽  
Body Size ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Structure ◽  
In Vitro Studies ◽  
Wild Type ◽  
Structure And Morphology

(miRNAs) inhibit bone formation by inhibiting the translation of specific genes. Several in vitro studies have suggested that miR-23a inhibits osteogenic differentiation by suppressing the translation of Runx2, a transcription factor essential for osteoblastogenesis, and of Satb2, a member of the special AT rich binding protein family. In the present study, we used a gain-of-function approach to determine the roles of miR-23a in bone formation and homeostasis in vivo. The miR-23a transgenic (Tg) mice grew normally and their body size and weight were similar to those of wild-type (WT) littermates. Bone structure and morphology were similar in Tg and WT mice. Furthermore, the numbers of osteoblasts and osteoclasts, as well as their activities in bone were similar between Tg and WT mice. Our results indicate that miR-23 has limited roles in bone formation and maintenance in vivo in mice.

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