NAP1L2 drives mesenchymal stem cell senescence and suppresses osteogenic differentiation

Hu, Menglan; Xing, Liangyu; Zhang, Li; Liu, Fan; Wang, Sheng; Xie, Ying; Wang, Jingjing; Jiang, Hongmei; Guo, Jing; Li, Xin; Wang, Jingya; Sui, Lei; Li, Changyi; Liu, Dayong; Liu, Zhiqiang

doi:10.1111/acel.13551

Cited by 41 publications

(39 citation statements)

References 31 publications

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“…YB-1 is a DNA/RNA-binding protein ( Lyabin, Eliseeva & Ovchinnikov, 2014 ), and has been reported to bind to the promoter region of p16 INK 4 A and inhibit the expression of p16 INK 4 A ( Kotake et al, 2013 ; Xiao et al, 2020 ), a maker of cellular senescence ( Ogrodnik et al, 2019 ; Omori et al, 2020 ). Furthermore, several studies have demonstrated that the expression of p16 INK 4 A is much higher in BMCSs of older mice than in young controls ( Hu et al, 2022 ; Li et al, 2017 ). To verify the interaction between YB-1 and Gm31629 in BMSCs, the RNA pull-down assay was repeated and the binding of Gm31629 to YB-1 in BMSCs was confirmed ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Long noncoding RNA Gm31629 promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity

Cai

Xiao

Yang

et al. 2022

PeerJ

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Background Long noncoding RNA Gm31629 can regulate hypothalamic neural stem cells (htNSCs) senescence and the aging process. However, the effect of Gm31629 on the senescence of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration is unclear. In the present study, we investigated the effects of Gm31629 on the senescence of BMSCs and bone regeneration. Methods Gm31629 knockout (Gm31629-KO) and wild-type (WT) mice were used to establish a bone regeneration model. The Brdu labelling, CCK8 assay, wound healing assay, β-gal staining and osteogenic differentiation assay were used to assess the effects of Gm31629 on the functions of BMSCs. Micro-computed tomography (CT), histochemical and immunohistochemical staining were used to evaluate the ability of bone regeneration. The mimic of Gm31629, theaflavin 3-gallate, was used to investigate its role on the senescence of BMSCs and bone regeneration. Results The expression of Gm31629 reduced in BMSCs of middle-aged mice was compared with that of young mice. The deletion of Gm31629 was sufficient to drive the senescence of BMSCs, resulting in impaired bone regeneration in mice. Mechanistically, Gm31629 could interact with Y-box protein 1(YB-1) and delay its degradation, decreasing the transcription of p16INK4A of BMSCs. We also found that theaflavin 3-gallate could alleviate the senescence of BMSCs and promote bone regeneration in middle-aged mice. Conclusion These results indicated that Gm31629 played an important role on BMSCs senescence and bone regeneration and provided a therapeutic target to promote bone regeneration.

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Section: Resultsmentioning

confidence: 99%

“…Recently, multiple studies have focused on the mechanism of BMSCs senescence ( Guo et al, 2021 ; Hu et al, 2022 ; Liu et al, 2021a ). The emerging roles of lncRNAs in regulating cellular senescence have also been documented in previous studies ( Lee et al, 2020 ; Xia et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA Gm31629 promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity

Cai

Xiao

Yang

et al. 2022

PeerJ

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“…Previous studies have found that NMN inhibited NAMPT and exacerbated inflammation [ 34 ]. There may be a bond between NMN and NAP1L2, the latter being able to regulate the deacetylation function of Sirt1 [ 35 ]. We observed that the expression of FN increased with the increase in NMN concentration.…”

Section: Discussionmentioning

confidence: 99%

NAD+ Anabolism Disturbance Causes Glomerular Mesangial Cell Injury in Diabetic Nephropathy

et al. 2022

IJMS

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The homeostasis of NAD+ anabolism is indispensable for maintaining the NAD+ pool. In mammals, the mainly synthetic pathway of NAD+ is the salvage synthesis, a reaction catalyzed by nicotinamide mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NNNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD+, respectively. However, the relationship between NAD+ anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD+ anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD+ levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD+ homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD+ anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.

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“…Nicotinamide mononucleotide is known to promote osteogenesis and reduce adipogenesis by regulating mesenchymal stromal cells via the SIRT1 pathway in aged bone marrow 21 . It has also been proved that NMN is capable of alleviating the rate of the β-galactosidase staining and telomere DNA damage in senescent bone marrow-derived stem cells (BMSCs) via interaction with the NAP1L2 protein 22 .…”

Section: Discussionmentioning

confidence: 99%

Impact of nicotinamide mononucleotide (NMN) and platelet rich fibrin (PRF) on senescence in spontaneously aging and irradiated human osteoblasts

Hakim

Gracht

Pries

et al. 2022

Preprint

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With the increasing human lifespan, bone aging and related pathologies increasingly contribute to the musculo-skelettal homeostasis, and senescence related osteoblasts disorders are supposed to play a key role in osteoporosis, osteonecrosis and bone remodeling diseases. Only limited studies have elucidated the histomorphological and molecular changes in senescent human osteoblasts (OBs) and their potential treatment.In the present study we investigated the cellular changes induced by spontaneous inherent as well as radiation-induced senescence in OBs and the impact of addition cultivation with nicotinamide mononucleotide (NMN) and platelet rich fibrin (PRF) on apoptosis, senescence-associated β-galactosidase staining and senescence related gene expression using RT2 Profiler PCR array. We found that OBs alteration through spontaneous inherent aging follows a different pathway than that of radiation-induced cellular senescence. Both NMN and PRF seem to provide a senescence and radioprotective effect on human OBs, albeit by different mechanisms. These results provide evidence on the potential clinical implication of systematic NMN administration and local PRF application to prevent age-related bone disturbance in elderly patients.

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NAP1L2 drives mesenchymal stem cell senescence and suppresses osteogenic differentiation

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 41 publications

References 31 publications

Long noncoding RNA Gm31629 promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity

Long noncoding RNA Gm31629 promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity

NAD+ Anabolism Disturbance Causes Glomerular Mesangial Cell Injury in Diabetic Nephropathy

Impact of nicotinamide mononucleotide (NMN) and platelet rich fibrin (PRF) on senescence in spontaneously aging and irradiated human osteoblasts

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