microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway

Meng, Yubin; Li, Xue; Li, Zhaoyang; Zhao, Jin; Yuan, Xubo; Ren, Yu; Cui, Zhenduo; Liu, Yunde; Yang, Xianjin

doi:10.1002/jor.22884

Cited by 105 publications

(81 citation statements)

References 30 publications

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“…In this study, we found that the early markers of osteogenesis-related genes, including COLI, COLIII, RUNX2, OPN, and OCN, were upregulated compared with the levels obtained with the naked MAO Ti surface on days 3, 6, and 9, and this upregulation profile presented a time-dependent pattern and a dose-dependent effect. Our results indicated that the coating of CS/HA/miR-21 nanoparticles on the MAO Ti surface via reverse transfection promotes osteogenic differentiation at the mRNA level, which is in accordance with previous studies 16,17 that found that the overexpression of miR-21 can facilitate osteogenesis and accelerate bone fracture healing; furthermore, its target PI3K-AKT-GSK3β pathway may play an important role in the osteogenic differentiation of cells by stabilizing β-catenin according to previous reports. 17 This study confirmed the feasibility of fabricating CS/HA/miR-21 nanoparticle-coated MAO Ti surfaces via reverse transfection and demonstrated their application for the transfection of miR-21 to adjust the fate of hBMMSCs in vitro.…”

supporting

confidence: 93%

“…Our results indicated that the coating of CS/HA/miR-21 nanoparticles on the MAO Ti surface via reverse transfection promotes osteogenic differentiation at the mRNA level, which is in accordance with previous studies 16,17 that found that the overexpression of miR-21 can facilitate osteogenesis and accelerate bone fracture healing; furthermore, its target PI3K-AKT-GSK3β pathway may play an important role in the osteogenic differentiation of cells by stabilizing β-catenin according to previous reports. 17 This study confirmed the feasibility of fabricating CS/HA/miR-21 nanoparticle-coated MAO Ti surfaces via reverse transfection and demonstrated their application for the transfection of miR-21 to adjust the fate of hBMMSCs in vitro. The focus of our next study will be to determine the in vivo effects of this miR-21 coating method, including the induction of osseointegration between an implant and the surrounding bone.…”

supporting

confidence: 93%

“…16 miR-21 has been found to be highly expressed during osteogenic differentiation, which indicates that this miRNA may repress stemness maintenance in osteoblasts. 16, 17 Ourania et al 18 and Meng et al 17 revealed that the overexpression of miR-21 can accelerate osteogenesis and impair adipogenesis in both human umbilical cord mesenchymal stem cells (MSCs) and human bone marrow MSCs (hBMMSCs); miR-21 may exert its osteogenic function through the PI3K-AKT-GSK3β pathway via the stabilization and accumulation of β-catenin. 17 A key issue in the therapeutic application of miRNAs is safe and highly efficient transfection.…”

Section: Introductionmentioning

confidence: 99%

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Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

Wang¹,

Wu²,

Feng³

et al. 2015

IJN

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Dental implants have been widely used for the replacement of missing teeth in the clinic, but further improvements are needed to meet the clinical demands for faster and tighter osseointegration. In this study, we fabricated safe and biocompatible chitosan (CS)/hyaluronic acid (HA) nanoparticles to deliver microRNA-21 (miR-21) and thereby accelerate osteogenesis in human bone marrow mesenchymal stem cells (hBMMSCs). The CS/HA/miR-21 nanoparticles were cross-linked with 0.2% gel solution onto microarc oxidation (MAO)-treated titanium (Ti) surfaces to fabricate the miR-21-functionalized MAO Ti surface, resulting in the development of a novel coating for reverse transfection. To characterize the CS/HA/miR-21 nanoparticles, their particle size, zeta potential, surface morphology, and gel retardation ability were sequentially investigated. Their biological effects, such as cell viability, cytotoxicity, and expression of osteogenic genes by hBMMSCs on the miR-21-functionalized MAO Ti surfaces, were evaluated. Finally, we explored appropriate CS/HA/miR-21 nanoparticles with a CS/HA ratio of 4:1 and N/P ratio 20:1 for transfection, which presented good spherical morphology, an average diameter of 160.4±10.75 nm, and a positive zeta potential. The miR-21-functionalized MAO Ti surfaces demonstrated cell viability, cytotoxicity, and cell spreading comparable to those exhibited by naked MAO Ti surfaces and led to significantly higher expression of osteogenic genes. This novel miR-21-functionalized Ti implant may be used in the clinic to allow more effective and robust osseointegration.

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supporting

confidence: 93%

supporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

Wang¹,

Wu²,

Feng³

et al. 2015

IJN

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“…Trohatou et al 25 revealed that overexpression of miR-21 could accelerate osteogenesis and impair adipogenesis in hBMMSCs, and Yang et al 34 validated that miR-21 could promote the osteoblast differentiation of hMMSCs by repressing SPRY1, which can negatively regulate the osteogenic differentiation of MSCs. Meng et al 35 also found that miR-21 could promote the osteogenic differentiation of human umbilical cord mesenchymal stem cells through the PI3K-AKT-GSK3β pathway via the stabilization and accumulation of β-catenin. Our study confirmed the feasibility of fabricating miR-21-delivered hBMMSC sheets on CS/HA/miR-21 NP-coated culture plates by reverse transfection, and the results demonstrated higher osteogenic differentiation capability than that of the undelivered groups.…”

mentioning

confidence: 98%

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Wang

Wu²,

Wei

et al. 2016

IJN

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Cell sheet engineering has emerged as a novel approach to effectively deliver seeding cells for tissue regeneration, and developing human bone marrow mesenchymal stem cell (hBMMSC) sheets with high osteogenic ability is a constant requirement from clinics for faster and higher-quality bone formation. In this work, we fabricated biocompatible and safe chitosan (CS)/hyaluronic acid (HA) nanoparticles (NPs) to deliver microRNA-21 (miR-21), which has been proved to accelerate osteogenesis in hBMMSCs; then, the CS/HA/miR-21 NPs were cross-linked onto the surfaces of culture plates with 0.2% gel solution to fabricate miR-21-functionalized culture plates for reverse transfection. hBMMSC sheets were induced continuously for 14 days using a vitamin C-rich method on the miR-21-functionalized culture plates. For the characterization of CS/HA/miR-21 NPs, the particle size, zeta potential, surface morphology, and gel retardation were sequentially investigated. Then, the biological effects of hBMMSC sheets on the miR-21-functionalized culture plates were evaluated. The assay results demonstrated that the hBMMSC sheets could be successfully induced via the novel reverse transfection approach, and miR-21 delivery significantly enhanced the in vitro osteogenic differentiation of hBMMSC sheets in terms of upregulating calcification-related gene expression and enhancing alkaline phosphatase production, collagen secretion, and mineralized nodule formation. The enhanced osteogenic activity of hBMMSC sheets might promisingly lead to more rapid and more robust bone regeneration for clinical use.

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“…While this enhancer has not been shown to be active in bone or connective tissue, the gene is known to regulate miR21 which is involved in stem cell to osteoblast differentiation. Further investigation would be required to establish if this SNP or the surrounding enhancer altered the control of Papd5 in fibro-osseous disease (Boele et al 2014; Meng et al 2015). Three further genes on Chr 8 ( Rpgrip1l , Chd9 , and Rbl2 ) contain CnSNPs which are predicted to change the functions of the gene products (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Genetic determinants of fibro-osseous lesions in aged inbred mice

Berndt

Ackert‐Bicknell

Silva

et al. 2016

Experimental and Molecular Pathology

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Fibro-osseous lesions in mice are progressive aging changes in which the bone marrow is replaced to various degrees by fibrovascular stroma and bony trabeculae in a wide variety of bones. The frequency and severity varied greatly among 28 different inbred mouse stains, predominantly affecting females, ranging from 0% for 10 strains to 100% for KK/HlJ and NZW/LacJ female mice. Few lesions were observed in male mice and for 23 of the strains, no lesions were observed in males for any of the cohorts. There were no significant correlations between strain-specific severities of fibro-osseous lesions and ovarian (r=0.11; P=0.57) or endometrial (r=0.03; P=0.89) cyst formation frequency or abnormalities in parathyroid glands. Frequency of fibro-osseous lesions was most strongly associated (P < 10−6) with genome variations on chromosome (Chr) 8 at 90.6 and 90.8 Mb (rs33108071, rs33500669; P = 5.0 · 10−10, 1.3 · 10−6), Chr 15 at 23.6 and 23.8 Mb (rs32087871, rs45770368; P = 7.3 · 10−7, 2.7 · 10−6), and Chr 19 at 33.2, 33.4, and 33.6 Mb (rs311004232, rs30524929, rs30448815; P=2.8 · 10−6, 2.8 · 10−6, 2.8 · 10−6) in genome-wide association studies (GWAS). The relatively large number of candidate genes identified in the GWAS analyses suggests that this may be an extremely complex polygenic disease. These results indicate that fibro-osseous lesions are surprisingly common in many inbred strains of laboratory mice as they age. While this presents little problem in most studies that utilize young animals, it may complicate aging studies, particularly those focused on bone.

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microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway

Cited by 105 publications

References 30 publications

Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Genetic determinants of fibro-osseous lesions in aged inbred mice

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