Spironolactone Ameliorates Senescence and Calcification by Modulating Autophagy in Rat Tendon‐Derived Stem Cells via the NF‐<i>κ</i>B/MAPK Pathway

Xu, Kai; Lin, Changjian; Ma, Daowei; Chen, Mengyao; Zhou, Xing; He, Yuzhe; Moqbel, Safwat Adel Abdo; Ma, Chiyuan; Wu, Lidong

doi:10.1155/2021/5519587

Cited by 19 publications

(13 citation statements)

References 57 publications

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“…[ 15 ] Recently, studies have observed that NF‐κB was activated in senescent TSPCs, which could contribute to the hypofunction of AT‐SCs. [ 16 ] Therefore, we explored whether SHED‐Exo bio‐nanoparticles could curb the activation of the NF‐κB signaling pathway. Treatment with SHED‐Exos in vitro inhibited the phosphorylation of p65 and nuclear translocation of p65 in AT‐SCs (Figure S3a,b, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

Jin¹,

Wang²,

Wu³

et al. 2023

Advanced Materials

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Tendon aging is frequently accompanied by extrinsic inflammation-aging harassment and intrinsic TSPC senescence, resulting in impaired reparative and regenerative capacities. [2] Although the functional decline of senescent TSPCs is accepted well, an efficient and precise method to rejuvenate aged TSPC (AT-SC) function and recover aging-impaired tendon reparative capacity remains to be further explored.Extracellular vesicles (EVs) are membrane-enclosed structures mainly that are classified into two main groups: exosomes and microvesicles. Among them, exosomes range from 40 to 150 nm in diameter and are mainly derived from the endosomal system, [3] whereas microvesicles range from 100 to 1000 nm in diameter and are generated by shedding of the plasma membrane. EVs could facilitate intercellular communication by transferring mRNA, microRNA, proteins, and organelle cargoes into recipient cells; [4] therefore, EVs have been suggested as excellent candidates for therapeutic methods for tissue regeneration and repair. Recently, EVs have been proven to be beneficial components of young blood in extending the life span of mice, suggesting that some specific EVs may possess an anti-senescent function. [5] Aging impairs tendon stem/progenitor cell function and tendon homeostasis, however, effective treatments for aging-induced tendon diseases are lacking. Exosomes are naturally derived nanoparticles that contain bioactive molecules, and therefore, have attracted great interest in tissue engineering and regenerative medicine. In this study, it is shown that young exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED-Exos) possess abundant anti-aging signals. These young bio-nanoparticles can alleviate the aging phenotypes of aged tendon stem/progenitor cells (AT-SCs) and maintain their tenogenic capacity. Mechanistically, SHED-Exos modulate histone methylation and inhibit nuclear factor-κB to reverse AT-SC aging. In a naturally aging mouse model, systemic administration of SHED-Exo bio-nanoparticles retards tendon degeneration. Interestingly, local delivery of SHED-Exos-loaded microspheres confers anti-aging phenotypes, including reduced senescent cells and decreased ectopic bone formation, thereby functionally and structurally rescuing endogenous tendon regeneration and repair capacity in aged rats. Overall, SHED-Exos, as natural bioactive nanoparticles, have promising translational and therapeutic potential for aging-related diseases.

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Section: Resultsmentioning

confidence: 99%

Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

Jin¹,

Wang²,

Wu³

et al. 2023

Advanced Materials

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“…NF-κB , which has already been shown to play a role in inflammation, is activated by pro-inflammatory cytokines, including TNFα and IFNγ. NF-κB expression is also dependent on IRF1 activation, and increased NF - κ B levels are detected in early RC tendinopathy [ 33 , 34 , 35 , 36 ]. In our study, NF - κ B was not significantly modulated by TNFα and IFNγ cytokines.…”

Section: Discussionmentioning

confidence: 99%

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Giancola

Oliva

Gallorini

et al. 2022

IJMS

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Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs.

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“…The senescence detected assay was conducted as previously described (Xu et al, 2021). Briefly, pretreated chondrocytes in 12-well plates were incubated with β-Galactosidase staining buffer for 24 h from β-Galactosidase activity assay (C0602, Beyotime Biotechnology, China) according to the manufacturer's instructions.…”

Section: β-Galactosidase Activity Assaymentioning

confidence: 99%

“…To further elucidate the underlying mechanism of NitC on RACs, several emerging bioinformatics were performed as our previous study (Xu et al, 2021). To begin with, PharmMapper was used to predict the potential protein targets directly binding with NitC.…”

Section: Nitc Was Capable Of Inhibiting Ros Generationmentioning

confidence: 99%

Nitidine Chloride Alleviates Inflammation and Cellular Senescence in Murine Osteoarthritis Through Scavenging ROS

Lin

Tang

et al. 2022

Front. Pharmacol.

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Osteoarthritis (OA) is one of the most common chronic musculoskeletal disorder worldwide, representing a major source of disability, pain and socioeconomic burden. Yet the effective pharmaceutical treatments applied in the clinical works are merely symptomatic management with uncertainty around their long-term safety and efficacy, namely no drugs currently are capable of modulating the biological progression of OA. Here, we identified the potent anti-inflammatory as well as anti-oxidative properties of Nitidine Chloride (NitC), a bioactive phytochemical alkaloid extracted from natural herbs, in IL-1β-treated rat articular chondrocytes (RACs), LPS-stimulated RAW 264.7 and rat osteoarthritic models in vivo. We demonstrated NitC remarkably inhibited the production of inflammatory mediators including COX2 and iNOS, suppressed the activation of MAPK and NF-κB cell signaling pathway and reduced the expression of extracellular matrix (ECM) degrading enzymes including MMP3, MMP9 and MMP13 in IL-1β-treated RACs. Several emerging bioinformatics tools were performed to predict the underlying mechanism, the result of which indicated the potential reactive oxygen species (ROS) clearance potential of NitC. Further, NitC exhibited its anti-oxidative potential through ameliorating cellular senescence in IL-1β-treated RACs and decreasing NLRP3 inflammasomes activation in LPS-stimulated RAW 264.7 via scavenging ROS. Additionally, X-ray, micro-CT and other experiments in vivo demonstrated that intra-articular injection of NitC significantly alleviated the cartilage erosion, ECM degradation and subchondral alterations in OA progression. In conclusion, the present study reported the potent anti-inflammatory and anti-oxidative potential of NitC in OA biological process, providing a promising therapeutic agent for OA management.

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Spironolactone Ameliorates Senescence and Calcification by Modulating Autophagy in Rat Tendon‐Derived Stem Cells via the NF‐κB/MAPK Pathway

Cited by 19 publications

References 57 publications

Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Nitidine Chloride Alleviates Inflammation and Cellular Senescence in Murine Osteoarthritis Through Scavenging ROS

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