Wnt5a/FZD4 Mediates the Mechanical Stretch-Induced Osteogenic Differentiation of Bone Mesenchymal Stem Cells

Gu, Qingguo; Tian, Haijun; Zhang, Kai; Chen, Deyu; Chen, Dechun; Wang, Xinwei; Zhao, Jie

doi:10.1159/000491721

Cited by 49 publications

(40 citation statements)

References 28 publications

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“…In vivo studies have shown that exercise increases bone mass, BMD and bone strength, and improves bone microstructure in both humans and animals [7,[26][27][28]. In vitro studies have also reported that mechanical loading enhances osteogenic differentiation and inhibits bone resorption through regulating bone anabolic and anti-catabolic gene expression, thus improving bone metabolism and promoting bone formation [9,29,30].…”

Section: Discussionmentioning

confidence: 99%

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

et al. 2019

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Exercise is an effective way to prevent osteoporosis, but its mechanism remains unclear. MicroRNAs (miRNAs) play an essential role in bone metabolism. Recently, mechanical loading was reported to induce changes in miRNA expression in osteoblasts. However, the role of miRNAs in bone under exercise and its underlining mechanisms of action still remain unknown. MiR-214 was reported to regulate the process of osteogenesis and is considered a biomarker of osteoporosis. In this study, we aimed to investigate whether exercise could induce changes in miRNA expression in bone and to study the effects of miR-214 on mechanical loading-induced osteogenesis in osteoblasts. The results showed that miR-214 was down-regulated in both tibia from C57BL/6 mice after exercise in vivo and in osteoblasts after mechanical strain in vitro. Mechanical strain could enhance the ALP activity, promote matrix mineralization, up-regulate the expression of osteogenic factors such as ATF4, Osterix, ALP and β-catenin, and down-regulate RANKL and RANK expression. Over-expression of miR-214 not only inhibited the expression of these osteogenic factors but also attenuated mechanical strain-enhanced osteogenesis in osteoblasts. Collectively, our results indicated that miR-214 could attenuate the osteogenic effects of mechanical loading on osteoblasts, suggesting that inhibition of miR-214 may be one of the ways in which exercise prevents osteoporosis.

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Section: Discussionmentioning

confidence: 99%

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

et al. 2019

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“…ALP staining assay was determined as reported . ALP staining was performed on cultured control and β‐GP‐treated cells.…”

Section: Methodsmentioning

confidence: 99%

“…2.8 | Alkaline phosphatase staining and activity assay ALP staining assay was determined as reported. 19 ALP staining was performed on cultured control and β-GP-treated cells. After being rinsed with PBS three times, the cell layer was fixed in 4% paraformaldehyde for 15 minutes at room temperature.…”

Section: Construction Of Recombinant Adenoviruses For Klotho and Fgf23mentioning

confidence: 99%

Klotho/FGF23 axis mediates high phosphate‐induced vascular calcification in vascular smooth muscle cells via Wnt7b/β‐catenin pathway

Chen

Huang

Duan

et al. 2019

The Kaohsiung J of Med Scie

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Vascular calcification (VC) plays as a critical role on cardiovascular disease (CVD) and acts as a notable risk factor in cardiovascular system. Vascular smooth muscle cells (VSMCs) calcification can be triggered by high phosphate treatment; however, the explicit mechanism remains unclear. In the present study, we isolated VSMCs from primary rat artery, applied β‐GP (β‐glycerophosphate) for inducing VSMCs calcification in vitro to explore the mechanism of phosphate‐induced calcification in VSMCs. Alizarin red staining was performed to assess the mineralization in VSMCs. Calcium deposition experiment was taken to evaluate the calcium content. ALP staining was determined to assess the ALP activity. The recombinant adenoviruses were constructed for the overexpression of Klotho and FGF23, respectively. qRT‐PCR and western blot analysis were subjected to measure the expression of Klotho/FGF23 and correlated genes among Wnt7b/β‐catenin pathway. We found that the calcium content was obviously increased and Alizarin red staining was positive in calcification group exposure with high phosphate in a time‐dependent manner. The expression of Klotho and FGF23 was significantly decreased in the calcification group. However, overexpression of Klotho and FGF23 markedly reversed VSMCs calcification stimulating with high phosphate treatment. Moreover, Wnt7b/β‐catenin inhibitor DKK1 could partly attenuate the effect of high phosphate on calcified VSMCs. These findings demonstrated that Klotho/FGF23 axis could modulate high phosphate‐induced VSMCs calcification via Wnt7b/β‐catenin signaling pathway. Our findings unravel that Klotho/FGF23‐ Wnt7b/β‐catenin axis functions as a crucial role in the VSMCs calcification.

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“…As a validation of our procedure, we found the 3 positive MSCs markers of ISCT among the selected annotated genes: THY1 (CD90), ENG (CD105), and NT5E (CD73). We also retrieved some influencers of MSCs activity, for example WNT5A [45,46], Lamin A/C [47], FAP [48] and others. The complete list of selected genes is provided in Table S5.…”

Section: Enrichment Of a Restricted Set Of Mlincs And Mloancsmentioning

confidence: 99%

Detailed analysis of public RNAseq data and long non-coding RNA: a proposed enhancement to mesenchymal stem cell characterisation

Riquier

Mathieu

Boureux

et al. 2020

Preprint

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The development of RNA sequencing (RNAseq) and corresponding emergence of public datasets have created new avenues of transcriptional marker search. The long non-coding RNAs (lncRNAs) constitute an emerging class of transcripts with a potential for high tissue specificity and function. Using a dedicated bioinformatics pipeline, we propose to construct a cell-specific catalogue of unannotated lncRNAs and to identify the strongest cell markers. This pipeline uses ab initio transcript identification, pseudoalignment and new methodologies such as a specific k-mer approach for naive quantification of expression in numerous RNAseq data.For an application model, we focused on Mesenchymal Stem Cells (MSCs), a type of adult multipotent stem-cells of diverse tissue origins. Frequently used in clinics, these cells lack extensive characterisation. Our pipeline was able to highlight different lncRNAs with high specificity for MSCs. In silico methodologies for functional prediction demonstrated that each candidate represents one specific state of MSCs biology. Together, these results suggest an approach that can be employed to harness lncRNA as cell marker, showing different candidates as potential actors in MSCs biology, while suggesting promising directions for future experimental investigations.

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Wnt5a/FZD4 Mediates the Mechanical Stretch-Induced Osteogenic Differentiation of Bone Mesenchymal Stem Cells

Cited by 49 publications

References 28 publications

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

Klotho/FGF23 axis mediates high phosphate‐induced vascular calcification in vascular smooth muscle cells via Wnt7b/β‐catenin pathway

Detailed analysis of public RNAseq data and long non-coding RNA: a proposed enhancement to mesenchymal stem cell characterisation

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