Age-Related Insulin-Like Growth Factor Binding Protein-4 Overexpression Inhibits Osteogenic Differentiation of Rat Mesenchymal Stem Cells

Wu, Jinhui; Wang, Chao; Xiong, Min; Wu, Yungang; Yuan, Jian; Ding, Muchen; Li, Jing‐Feng; Shi, Zhi-Cai

doi:10.1159/000477873

Cited by 21 publications

(16 citation statements)

References 35 publications

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“…Silencing mitofusin-2 has been found to inhibit MSC senescence induced by the abrogation of FGF21 as well. Knockdown of insulin-like growth factor binding protein 4 restored the osteogenic potency of aged MSCs via the activation of Erk and Smad signals[ 110 ]. Pretreatment of aged MSCs with macrophage migration inhibitory factor (MIF) enhanced the secretion of vascular endothelial growth factor (VEGF), bFGF, hepatocyte growth factor, and insulin-like growth factor, which promoted their growth, paracrine function, and survival[ 80 ].…”

Section: Cellular Rejuvenation Strategiesmentioning

confidence: 99%

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Meng¹,

Liu²,

Lu³

et al. 2020

WJSC

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Mesenchymal stem/stromal cells (MSCs) have various properties that make them promising candidates for stem cell-based therapies in clinical settings. These include self-renewal, multilineage differentiation, and immunoregulation. However, recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products. Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs. This review will summarize the current knowledge on characteristics and functional changes of aged MSCs. Additionally, it will highlight cell rejuvenation strategies such as molecular regulation, non-coding RNA modifications, and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.

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Section: Cellular Rejuvenation Strategiesmentioning

confidence: 99%

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Meng¹,

Liu²,

Lu³

et al. 2020

WJSC

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“…IGFBP4 can act as an inhibitor of the canonical Wnt signaling required for cardiogenesis and provides a molecular link between IGF signaling and Wnt signaling [31]. There is evidence that IGFBP4 expression increases with age and is associated with the impairment of MSC differentiation via the Erk and Smad pathway [32]. Consistent with previous studies that indicated IGFBP4 as a key component needed for triggering senescence in young MSC and a harmful factor that impair the habituation learning, which is correlated with cognitive function [20, 33], our present study demonstrated that IGFBP4 was up-regulated in the plasma of aged compared with young subjects and that injection of IGFBP4 into mice also accelerates cognitive dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey

et al. 2019

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Background The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein. Results Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice. Conclusions This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.

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“…Secreted by β cells of the pancreas, insulin is a potent anabolic hormone in stem cell differentiation and bone formation (Wu et al 2017). Interestingly, at the early stage of osteogenic differentiation of MC-3T3 cells (days 3 to 6), IGF-I and IGFBP-2 activated the AMPK pathway and enhanced the phosphorylation of ULK-1 S555 (a known AMPK phosphorylation site in ULK-1 that is necessary to assemble the essential components of autophagosome) and the expression of beclin-1 and LC3-II, which indicated the stimulation of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Signals in Stem Cell Differentiation on Fluorapatite-Modified Scaffolds

Guo

Cao

et al. 2018

J Dent Res

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Previously, we reported that the fluorapatite (FA)-modified polycaprolactone (PCL) nanofiber could be an odontogenic/osteogenic inductive tissue-engineering scaffold by inducing stem cell differentiation and mineralization. The present study aimed to explore which of the signal pathways affected this differentiation and mineralization process. The Human Signal Transduction PathwayFinder RT Profiler PCR Array was used to analyze the involvement of potential signal transduction pathways during human dental pulp stem cell (DPSCs) osteogenic differentiation induced by FA-modified PCL nanofiber scaffolds. Based on the results, perturbation studies of the signaling pathways hedgehog, insulin, and Wnt were performed. Moreover, the autophagy process was studied, as indicated by the expression of the microtubule-associated protein 1 light chain 3A/B-II (LC3-II) and the cell osteogenic phenotypic changes. In a comparison of the cells grown on PCL + FA scaffolds and those on PCL-only scaffolds, the transcript expression of BMP2, BMP4, FOXA2, PTCH1, WNT1, and WNT2 (PCR array-labeled signal proteins of the hedgehog pathway); CEBPB, FASN, and HK2 (PCR array-labeled signal proteins of the insulin pathway); and CCND1, JUN, MYC, TCF7, and WISP1 (PCR array-labeled signal proteins of the Wnt pathway) doubled at day 14 when obvious cell osteogenic differentiation occurred. Phenotypically, in all the perturbation groups at day 14, ALP activity, OPN, and autophagy marker LC3-II expression were coincidently decreased. Consistently, no positive alizarin red staining or von Kossa staining was observed in the specimens from these perturbation groups at day 28. The results showed that when obvious cell differentiation occurred at day 14 on PCL + FA control groups, the inhibition of the hedgehog, insulin, and Wnt pathways significantly decreased DPSC osteogenic differentiation and mineralization. The osteogenic differentiation of DPSCs grown on FA-modified PCL scaffolds appeared to be positively modulated by the hedgehog, insulin, and Wnt signal pathways, which were coordinated with and/or mediated by the cell autophagy process.

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Age-Related Insulin-Like Growth Factor Binding Protein-4 Overexpression Inhibits Osteogenic Differentiation of Rat Mesenchymal Stem Cells

Cited by 21 publications

References 35 publications

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey

Signals in Stem Cell Differentiation on Fluorapatite-Modified Scaffolds

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