MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss

Chen, Zhihao; Huai, Ying; Chen, Gaoyang; Zhang, Yan; Li, Dijie; Zhao, Fan; Chen, Xiaofeng; Mao, Wenjing; Wang, Xuehao; Chen, Yin; Yang, Chaofei; Xu, Xia; Ru, Kang; Deng, Xiaoni; Hu, Lifang; Liu, Yu; Peng, Songlin; Zhang, Ge; Lin, Xiuping; Qian, Airong

doi:10.7150/ijbs.71411

Cited by 15 publications

(10 citation statements)

References 55 publications

(109 reference statements)

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“…Research has been demonstrated that miRNAs have many biological functions and participate in various cellular activities, including multidirectional differentiation and proliferation (Chen et al, 2022; He et al, 2019; Li et al, 2018). Many of these miRNAs are involved in osteogenic differentiation of cells.…”

Section: Discussionmentioning

confidence: 99%

“…For example, miR‐19b‐3p inhibits IGF‐1 expression, thereby preventing the differentiation of BMSCs into osteoblasts, leading to the development of osteoporosis (Yu et al, 2022). MiR‐138‐5p contributes to bone loss in the elderly by downregulating MACF1 expression and inhibiting osteogenic differentiation (Chen et al, 2022). MiR‐141‐3p overexpression is downregulated in ox‐LDL‐induced VSMCs, and its upregulation inhibits VSMC proliferation (Zhang et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we found that iRoot SP at the previously described optimal concentration participated in the miR‐141‐3p/MAPK pathway and induced the osteogenic differentiation of hSCAPs. OCN, OSX, RUNX2 and DSPP are the specific markers of osteogenic differentiation (Chen et al, 2022; Wu et al, 2020; Wu, Xue et al, 2021, Wu, Yang et al, 2021). On Day 3 of incubation, OCN expression in the miR‐141‐3p mimic group was not significantly lower than that in the mimic‐NC group.…”

Section: Discussionmentioning

confidence: 99%

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The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway

Xue

et al. 2023

Int Endodontic J

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AimThe premixed bioceramic sealer iRoot SP that is widely used clinically has been reported to kill bacterial biofilms and promote osteogenic differentiation of human stem cells from the apical papilla (hSCAPs). Although miR‐141‐3p has been substantiated to be involved in the osteogenic process, the underlying mechanisms remain unclear. The aim of this study was to investigate the role of miR‐141‐3p in osteogenic differentiation and underlying mechanisms of iRoot SP‐treated hSCAPs.MethodologyhSCAPs were extracted from tissue blocks with enzyme digestion and identified by using immunofluorescence, flow cytometry and alizarin red staining. The mRNA expression level of miR‐141‐3p in hSCPAs after culture with iRoot SP was examined by quantitative real‐time PCR (qRT‐PCR) assay. SPAG9 was identified as a downstream target gene of miR‐141‐3p by dual‐luciferase report assay. Alkaline phosphatase (ALP) staining and activity detection, alizarin red staining, calcium concentration assay, qRT‐PCR and western blot were used to estimate osteogenic differentiation ability and involved protein expression levels of the osteogenic makers and signalling pathway‐related factors in iRoot SP‐treated hSCAPs. Data were analysed by one‐way anova and post hoc Tukey's test to determine any statistical differences between the experimental groups and the control group. p < .05 was considered statistically significant.ResultsExpression of miR‐141‐3p was reduced in iRoot SP‐treated hSCAPs with the increased exposure time up to 7 days, and the western blot and qRT‐PCR results revealed that the osteogenic markers osteocalcin (OCN), osterix (OSX), runt‐related transcription factor 2 (RUNX2) and dentin sialophosphoprotein (DSPP) were inversely correlated with miR‐141‐3p. The negative regulatory relationship between miR‐141‐3p and SPAG9/ mitogen‐activated protein kinases (MAPK) signalling axis was validated in this in vitro experiments.ConclusionsThe bioceramic sealer iRoot SP promoted osteogenic differentiation of hSCAPs by inhibiting miR‐141‐3p following down‐regulated SPAG9 expression, and activated MAPK pathway. These findings proposed a novel therapeutic impact of bioceramic sealer iRoot SP inducing bone regeneration in refractory periapical periodontitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway

Xue

et al. 2023

Int Endodontic J

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“…This aligns with a number of studies underscoring the multiple pathways through which antagomiR‐138 can induce osteogenic differentiation. Suppressing miR‐138 expression in human [ 67 ] and primary calvaria osteoporotic osteoblasts [ 68 ] resulted in enhanced expression of osteogenic genes (Runx2, Osterix, ALP, and OC), greater ALP production, and increased mineralization. Similarly, Chen et al explored the osteogenic potential of antagomiR‐138 by reporting its stimulatory effect on the osteogenic differentiation of MC3T3‐E1, a mouse osteoblastic cell line.…”

Section: Discussionmentioning

confidence: 99%

A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles

Sadowska,

Power,

Genoud

et al. 2023

Advanced Materials

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Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long‐term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi‐faceted solution would will eradicate bacterial infection without long‐term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen‐based scaffold that addresses these needs by leveraging the potential of antibiotic‐free antimicrobial nanoparticles (copper‐doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA‐based gene therapy (utilizing an inhibitor of microRNA‐138) to stimulate both osteogenesis and angiogenesis, is developed. CuBG scaffolds reduce the attachment of gram‐positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR‐138 nanoparticles induce osteogenesis of human mesenchymal stem cells in vitro and heal a large load‐bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies results in a multifunctional antagomiR‐138‐activated CuBG scaffold inducing hMSC‐mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyzes killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi‐functional strategy for treating and repairing complex bone infections.

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“…With the increasing number of elderly individuals, there has been a significant rise in the prevalence of bone-related diseases worldwide [ 1 ]. Annually, over six million fractures occur globally, with 56 % requiring permanent or temporary internal fixation materials for surgical treatment [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Study on the mechanism of magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair

Nie,

Shi,

Wang

et al. 2024

Heliyon

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MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss

Cited by 15 publications

References 55 publications

The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway

The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway

A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles

Study on the mechanism of magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair

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