Exosomes derived from human urine–derived stem cells ameliorate IL-1β-induced intervertebral disk degeneration
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ABSTRACT:
SUBMITTER: Qian G
PROVIDER: S-EPMC11241922 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Intervertebral disk degeneration (IDD) is the major cause of low back pain (LBP), which affects 80% of the world's population. Interleukin 1 beta (IL-1β) is a major inflammatory factor that accelerates disk degeneration, and IL-1β levels increase in degenerative disks. It has recently been reported that luteoloside-a type of flavonoid glycoside-has anti-inflammatory properties. In the present study, we investigated the protective potential of luteoloside in IDD. We found that luteoloside maintains cell morphology and inhibits apoptosis (indicated by the reduced expression of cleaved caspase 3) in IL-1β-treated nucleus pulposus (NP) cells. It also suppresses inflammatory mediators-nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)-in IL-1β-treated NP cells. Furthermore, we found increased collagen II and aggrecan expression and reduced MMP13 and ADAMTS5 expression in luteoloside-treated NP cells in the presence of IL-1β. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved in apoptosis, inflammation, and extracellular matrix (ECM) homeostasis. Mechanistic studies revealed that the NF-κB signaling pathway is inhibited by luteoloside, and Nrf2 is involved in the regulation of luteoloside in NF-κB signaling because Nrf2 knockdown reduced the suppressive effect of luteoloside on NF-κB signaling. We also established a puncture-induced rat IDD model and demonstrated that the persistent intraperitoneal injection of luteoloside ameliorates the progression of IDD. In conclusion, we demonstrated that luteoloside activates the Nrf2/HO-1 signaling axis and is a potential therapeutic medicine for IDD.
| S-EPMC6690034 | biostudies-literature
Project description:PurposeTo investigate the association of polymorphism of IL-1β rs16944(T/C) with intervertebral disk degeneration (IDD), explore the possible mechanism and evaluate the predictive value of IL-1β for IDD.Patients and methodsA total of 196 consecutive patients with IDD were recruited, and 196 healthy controls were matched to these patients based on sex and age (±3 years). The polymorphisms of IL-1β rs16944(T/C), rs1143623(G/C), rs10490571(T/C) and rs2853550(A/G) were determined, and serum IL-1β, MMP-1, MMP-3, MMP-9 and a disintegrin-like and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) levels were measured. Univariate analysis was performed with Student t-test or one-way ANOVA followed by post hoc and Chi-square test. Variables with two-sided P<0.10 were included in multivariate analysis, which employed a backward stepwise logistic regression model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value.ResultsMultivariate analysis showed that the polymorphism of IL-1β rs16944(T/C) was independently associated with IDD. The risk for IDD was significantly increased in TT and TC genotype compared with CC genotype, and the OR of TT genotype was higher than that of TC genotype. ANOVA analysis showed that serum concentration of IL-1β was highest in IL-1β rs16944 TT genotype, intermediate in TC genotype, and lowest in CC genotype. Similarly, serum concentrations of MMP-3 and ADAMTS-4 demonstrated the same tendency of TT > TC > CC genotype. Serum concentrations of MMP-1 and MMP-9 were higher in TT genotype than in TC and CC genotype. The area under curve (AUC) of IL-1β levels in predicting IDD was 0.788 (SE: 0.023, P=0.001, 95% CI: 0.742-0.834), and the predictive value was modest with a sensitivity of 77.0% and a specificity of 75%.ConclusionPolymorphism of IL-1β rs16944(T/C) affected IDD susceptibility through upregulation of serum levels of IL-1β and subsequent stimulation of ECM degradation. IL-1β levels could be applied in predicting IDD.
| S-EPMC8163728 | biostudies-literature
Project description:Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies. These models help our understanding of the disease process, but are limited as they do not come close to replicating the complexities that exist with an in Vivo model. Animal models have been developed to help us gain further understanding of the degenerative cascade of IVD degeneration In Vivo and test experimental treatment modalities to either prevent or reverse the process of DDD. Many modalities for treatment of DDD have been developed including therapeutic protein injections, stem cell injections, gene therapy, and tissue engineering. These interventions have had promising outcomes in animal models. Several of these modalities have been attempted in human trials, with early outcomes having promising results. Further, increasing our understanding of the degenerative process is essential to the development of new therapeutic interventions and the optimization of existing treatment protocols. Despite limited data, biological therapies are a promising treatment modality for DDD that could impact our future management of low back pain.
| S-EPMC5585783 | biostudies-other
Project description:Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance of the anabolic and catabolic processes in the intervertebral disc, leading to an alteration in the composition of the extracellular matrix (ECM), loss of nucleus pulposus (NP) cells, excessive oxidative stress and inflammation. Degeneration of the IVD occurs naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression. IVDD, often referred to as degenerative disc disease (DDD), poses an increasingly substantial financial burden due to the aging population and increasing incidence of obesity in the United States. Current treatments for IVDD include pharmacological and surgical interventions, but these lack the ability to stop the progression of disease and restore the functionality of the IVD. Biological therapies have been evaluated but show varying degrees of efficacy in reversing disc degeneration long-term. Stem cell-based therapies have shown promising results in the regeneration of the IVD, but face both biological and ethical limitations. Exosomes play an important role in intercellular communication, and stem cell-derived exosomes have been shown to maintain the therapeutic benefit of their origin cells without the associated risks. This review highlights the current state of research on the use of stem-cell derived exosomes in the treatment of IVDD.
| S-EPMC8471333 | biostudies-literature
Project description:ObjectiveHuman bone marrow mesenchymal stem cell (hBMSC)-derived exosomes exhibit protective effects against inflammatory diseases. This study aimed to explore the effects of hBMSC-derived exosomes on osteoarthritis (OA) in vitro and its related mechanisms.Materials and methodsIn this experimental study, we characterised exosomes derived from hBMSCs by transmission electron microscopy, nanoparticle tracking and Western blot analysis. Cellular uptake of exosomes was observed by fluorescent microscopy. Cell viability of chondrocytes exposed to interleukin-1 beta (IL-1β) was determined by the Cell Counting Kit-8 (CCK-8). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine expression levels of genes related to apoptosis, inflammation, cartilage collagen metabolism and mitogen-activated protein kinases.ResultsFluorescence microscopy revealed that hBMSC-derived exosomes could be taken up by chondrocytes. hBMSC-derived exosomes could significantly enhance cell viability of chondrocytes in response to IL-1β treatment. RT-qPCR showed significant up-regulation of Survivin, Versican, IL-1β, IL-6, NF-κB, MMP-13, MAPK p38, JNK, ERK, Aggrecan and SOX9 expression levels by IL-1β treatment, while their mRNA expression levels decreased after coculture with exosomes. The anti-inflammatory gene TGF-β was markedly suppressed by IL-1β treatment; however, we observed its expression after co-culture with exosomes. Additionally, the pro-inflammatory genes IL-1β, IL-6, NF-κB, TNF-α and TNF-β displayed significantly elevated expression levels in the IL-1β group and reduced expression levels after co-culture with exosomes.ConclusionhBMSC-derived exosomes may play a protective role in chondrocytes through inhibiting cell apoptosis and the inflammatory response. These results will provide a novel therapeutic strategy for OA.
| S-EPMC8405079 | biostudies-literature
Project description:Mitochondrial dysfunction causes the production of reactive oxygen species (ROS) and oxidative damage, and oxidative stress and inflammation are considered key factors causing intervertebral disc degeneration (IVDD). Thus, restoring the mitochondrial dysfunction is an attractive strategy for treating IVDD. Platelet-derived extracellular vesicles (PEVs) are nanoparticles that target inflammation. Moreover, the vesicles produced by platelets (PLTs) have considerable anti-inflammatory effects. We investigate the use of PEVs as a therapeutic strategy for IVDD in this study. We extract PEVs and evaluate their properties; test their effects on H2O2-induced oxidative damage of nucleus pulposus (NP) cells; verify the role of PEVs in repairing H2O2-induced cellular mitochondrial dysfunction; and demonstrate the therapeutic effects of PEVs in a rat IVDD model. The results confirm that PEVs can restore impaired mitochondrial function, reduce oxidative stress, and restore cell metabolism by regulating the sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)-mitochondrial transcription factor A (TFAM) pathway; in rat models, PEVs retard the progression of IVDD. Our results demonstrate that the injection of PEVs can be a promising strategy for treating patients with IVDD.
| S-EPMC9758573 | biostudies-literature
Project description:Intervertebral disk degeneration (IDD) is strongly associated with genetic predisposition and environmental susceptibility. Several studies been conducted to investigate the potential association between IDD and FokI polymorphism located in the gene encoding the vitamin D receptor (VDR), and inconsistent conclusions had been reached among different ethnic populations. In order to assess the association between the FokI polymorphism and the risk of IDD, we performed a comprehensive and systematic meta-analysis. Candidate articles were retrieved from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and China Biology Medical (CBM) with strict inclusion criteria in January 2015. Among the 54 articles that were retrieved, only eight studies met the inclusion criteria. The pooled data analysis based on allele contrast, homozygote, heterozygote, dominant, and recessive models revealed no significant correlation between the FokI polymorphism and the risk of IDD. However, when stratified by ethnicity, significant associations were detected for Hispanics based on allele contrast (OR=1.395, 95% CI=1.059-1.836, P=0.018), homozygote (OR=1.849, 95% CI=1.001-3.416, P=0.049), heterozygote (OR=1.254, 95% CI=1.049-1.498, P=0.013), and dominant (OR=1.742, 95% CI=1.174-2.583, P=0.006) models, and for Asians using the dominant model (OR=1.293, 95% CI=1.025-1.632, P=0.030), whereas there is no significant association detected for Caucasians. In conclusion, FokI polymorphism is not generally associated with IDD, but there is increased risk for IDD in Hispanics and Asians carrying FokI allele T.
| S-EPMC4747649 | biostudies-literature
Project description:The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. IDD progresses with age, leading to spondylosis, spondylarthrosis, intervertebral disk herniation, and spinal stenosis. The purpose of this review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines in IDD and to appreciate the prognostic value of cytokine imbalance as its biomarker. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to the maintenance or alteration of cytokine balance may be a new key to unlocking the mystery of IDD development and new therapeutic strategies for the treatment of IDD in the setting of acute and chronic inflammation. The presented data support the hypothesis that cytokine imbalance is one of the most important biomarkers of IDD.
| S-EPMC9917299 | biostudies-literature
Project description:Intervertebral disks are biologically regulated by the maintenance of a balance between the anabolic and catabolic activities of disk cells. Therapeutic agents, initially evaluated using in vitro studies on disk cells and explants, have been used as intradiscal injections in preclinical settings to test in vivo efficacy. These include anabolic growth factors, other biostimulatory agents, and antagonistic agents against matrix-degrading enzymes and cytokines. Additional work is needed to identify patient populations, using methods such as MRI, and to better understand the mechanism of healing. Clinical trials are underway for a few of these agents and other promising candidates are on the horizon.
| S-EPMC4029337 | biostudies-literature
Project description:Intervertebral disk degeneration (IVDD) is a leading cause of disability. The degeneration is inevitable, and the mechanisms are complex. Current therapeutic strategies mainly focus on the relief of symptoms, not the intrinsic regeneration of the intervertebral disk (IVD). Tissue engineering is a promising strategy for IVDD due to its ability to restore a healthy microenvironment and promote IVD regeneration. This review briefly summarizes the IVD anatomy and composition and then sets out elements of the microenvironment and the interactions. We rationalized different scaffolds based on tissue engineering strategies used recently. To fulfill the complete restoration of a healthy IVD microenvironment, we propose that various tissue engineering strategies should be combined and customized to create personalized therapeutic strategies for each individual.
| S-EPMC8329559 | biostudies-literature