The effects of biophysical stimulation on osteogenic differentiation and the mechanisms from <scp>ncRNAs</scp>

Mao, Liwei; Guo, Jianmin; Hu, Linghui; Li, Lexuan; Xu, Jiake; Zou, Jun

doi:10.1002/cbf.3650

Cited by 6 publications

(6 citation statements)

References 129 publications

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“…Previous studies showed that mechanical stimuli induce intramembranous and endochondral ossification, and promote fracture healing [49]. In addition, biophysical stimuli such as mechanical strain, fluid shear stress (FSS), microgravity and vibration regulate non-coding RNA expression, thereby regulating the process of osteogenic differentiation [50,51]. Piezo1 as a major mechanosensor is necessary for mechanical stimulation to promote bone formation [21,50].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, biophysical stimuli such as mechanical strain, fluid shear stress (FSS), microgravity and vibration regulate non-coding RNA expression, thereby regulating the process of osteogenic differentiation [50,51]. Piezo1 as a major mechanosensor is necessary for mechanical stimulation to promote bone formation [21,50]. Therefore, Piezo1 can act as a promising therapeutic target to promote fracture healing.…”

Section: Discussionmentioning

confidence: 99%

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Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

Liu¹,

Tian²,

Hu³

et al. 2022

Int. J. Biol. Sci.

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The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periosteal stem cells (PSCs) and their derived osteoblastic lineage cells and chondrocytes. Furthermore, downregulation of Piezo1 in callus leads to impaired fracture healing, while activation by its specific agonist promotes fracture healing through stimulation of PSC-modulated chondrogenesis and osteogenesis, along with accelerated cartilage-to-bone transformation. Interestingly, vascular endothelial growth factor A is upregulated after Yoda1 treatment of PSCs, indicating an indirect role of Piezo1 in angiogenesis. Mechanistically, activation of Piezo1 promotes expression of Yes-associated protein (YAP) and its nuclear localization in PSCs, which in turn increases the expression and nuclear localization of β-catenin. In detail, YAP directly interacts with β-catenin in the nucleus and forms a transcriptional YAP/β-catenin complex, which upregulates osteogenic, chondrogenic and angiogenic factors. Lastly, Yoda1 treatment significantly improves fracture healing in a delayed union mouse model generated by tail suspension. These findings indicate that Piezo1 is a potential therapeutic target for fracture delayed union or nonunion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

Liu¹,

Tian²,

Hu³

et al. 2022

Int. J. Biol. Sci.

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“…According to a study by Li et al [ 34 ], lncRNA-H19 sponging miRNA-141 could modulate osteogenesis in nude mice models as well as in stem cells from apical papilla cultured in vitro . Interestingly, the expression of noncoding RNAs during osteogenic differentiation can be regulated by different biophysical stimuli, such as mechanical strain, fluid shear stress, or microgravity, followed by upregulation or downregulation of osteoblast differentiation-related genes [ 11 ]. Additionally, increasing evidence has demonstrated that osteogenic differentiation of MSCs can be genetically manipulated by various transcription factors, such as myocardin-related transcription factor A [ 35 ], zinc finger E-box-binding homeobox 1 [ 36 ], and T-Box20 [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, hDPSCs have been reported to exhibit a similar or even higher osteogenic potential compared with bone marrow mesenchymal stem cells (BMSCs) [6][7][8][9]. Numerous previous studies have reported that the osteogenic capacity of MSCs can be regulated by many factors [10,11], including noncoding RNA, transcription factors, bioactive materials, and various different biophysical stimuli.…”

Section: Introductionmentioning

confidence: 99%

ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways

et al. 2022

Stem Cell Res Ther

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Background The repair of cranio-maxillofacial bone defects remains a formidable clinical challenge. The Ets variant 2 (ETV2) transcription factor, which belongs to the E26 transformation-specific (ETS) family, has been reported to play a key role in neovascularization. However, the role of ETV2 in the osteogenesis of human dental pulp stem cells (hDPSCs) remains unexplored. Methods Transgenic overexpression of ETV2 was achieved using a lentiviral vector, based on a Dox-inducible system. The effects of Dox-induced overexpression of ETV2 on the osteogenesis of hDPSCs were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunofluorescence staining, alkaline phosphatase (ALP) staining, and Alizarin Red S (ARS) staining. Additionally, RNA-sequencing (RNA-Seq) analysis was performed to analyze the underlying mechanisms of ETV2-induced osteogenesis. Additionally, the role of ETV2 overexpression in bone formation in vivo was validated by animal studies with a rat calvarial defect model and a nude mice model. Results Our results demonstrated that ETV2 overexpression significantly upregulated the mRNA and protein expression levels of osteogenic markers, markedly enhanced ALP activity, and promoted matrix mineralization of hDPSCs. Moreover, the results of RNA-Seq analysis and western blot showed that the ERK/MAPK and PI3K-Akt signaling pathways were activated upon transgenic overexpression of ETV2. The enhanced osteogenic differentiation of hDPSCs due to ETV2 overexpression was partially reversed by treatment with inhibitors of ERK/MAPK or PI3K-AKT signaling. Furthermore, the results of in vivo studies demonstrated that ETV2 overexpression improved bone healing in a rat calvarial defect model and increased ectopic bone formation in nude mice. Conclusions Collectively, our results indicated that ETV2 overexpression exerted positive effects on the osteogenesis of hDPSCs, at least partially via the ERK/MAPK and PI3K/AKT signaling pathways.

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“…There is abundant evidence that non‐coding RNA plays a crucial role in the proliferation and differentiation of osteoblasts and bone marrow stromal cells. 40 For example, LncRNA HOTTIP accelerates osteogenic differentiation by interacting with TAF15 to stabilize DLX2. 41 LncRNA KCNQ1OT1 promotes osteogenic differentiation through miR‐205‐5p/RICTOR axis.…”

Section: Discussionmentioning

confidence: 99%

LncRNA TM1‐3P Regulates Proliferation, Apoptosis and Inflammation of Fibroblasts in Osteoarthritis through miR‐144‐3p/ONECUT2 Axis

Yang

et al. 2022

Orthopaedic Surgery

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Objective This study explores LncRNA TM1‐3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism. Methods Bioinformatics was performed to analyze OA disease‐related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1‐3P and miR‐144‐3p, ONECUT2 and miR‐144‐3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin–eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT‐qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one‐way analysis of variance of repeated measurement data was applied for multi‐group comparison, following Tukey's post‐test. Results ONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1‐3P were increased, and expression of miR‐144‐3p was decreased in interleukin (IL)‐1β‐induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR‐144‐3p down‐regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL‐1β (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1‐3P up‐regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR‐144‐3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1‐3P attenuated the injury of knee joint tissue, down‐regulated the expression of ONECUT2, Smurf2, IL‐1β, IL‐6, TNF‐α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05). Conclusion LncRNA TM1‐3P improved inflammation and damage of knee joints in OA rats through miR‐144‐3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA.

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The effects of biophysical stimulation on osteogenic differentiation and the mechanisms from ncRNAs

Cited by 6 publications

References 129 publications

Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways

LncRNA TM1‐3P Regulates Proliferation, Apoptosis and Inflammation of Fibroblasts in Osteoarthritis through miR‐144‐3p/ONECUT2 Axis

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