Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 12, 2025

Bone-related diseases impact a large portion of the global population and, due to their high disability rates and limited treatment options, pose significant medical economic challenges. Mesenchymal stem cells (MSCs) can differentiate into multiple cell types offer strong regenerative potential, making them promising for treating various diseases. However, issues with immune response survival limit effectiveness transplantation. This has led increased interest in cell-free therapy, particularly use exosomes, which is most studied form this approach. Exosomes are extracellular vesicles that contain proteins, lipids, nucleic acids play key role communication material exchange. Pyroptosis, death involved innate immunity, also associated many Studies have shown MSC-derived exosomes therapeutic potential range conditions by regulating inflammation pyroptosis. study explored modulating pyroptosis improve bone-related

Language: Английский

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Mitochondrial DNA variation and intervertebral disc degeneration: a genotypic analysis in a South African cohort

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 7, 2025

Non-communicable diseases are multifactorial in that they can be caused by genetic factors, age, sex and poor lifestyle choices. They estimated to account for 71% of deaths globally with 80% these occurring low- middle-income countries. This is particularly true Intervertebral Disc Degeneration associated mitochondrial dysfunction. Interestingly, dysfunction arise from mutations both the nuclear genomes. The present study, therefore, aimed determine if there an association between DNA disc degeneration a South African cohort, addition, generate data understudied populations. Mutations were selected using systematic literature review. was collected buccal swabs extracted standard salt-lysis protocol. Mass-array genotyping done previously reported as well novel mutations. GenAlEx (version 6.5), RStudio SHEsis used statistical analyses. Although no significant associations found, identified polymorphic C16223T, A10398G A8536G found have higher mutant allele frequencies case individuals indicating had larger cohort been used, significance may observed. study able genotypic information Furthermore, identification highlights importance considering future studies cohort.

Language: Английский

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Regulating macrophage phenotypes with IL4I1-mimetic nanoparticles in IDD treatment

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 6, 2025

Intervertebral disc degeneration (IDD) is a degenerative spinal condition characterized by structural damage, narrowing of joint spaces, and nerve root compression, significantly reducing patients' quality life. To address this challenge, novel therapeutic strategy was developed using cellulose supramolecular hydrogel as carrier to deliver IL4I1-modified MΦ membrane biomimetic nanoparticles (CHG@IL4I1-MNPs) target tissues. This exhibits excellent biocompatibility mechanical properties while enabling sustained drug release in the microenvironment, enhancing outcomes. CHG@IL4I1-MNPs effectively regulate polarization promoting M2 activation, thereby improving immune microenvironment balance. Animal studies demonstrated that alleviated symptoms IDD, reduced inflammation, supported tissue repair, highlighting its potential reduce reliance on long-term medication improve The uniquely combines nanoparticle technology with immunomodulation, achieving precise targeting MΦs. Beyond approach offers applications other immune-related diseases, providing versatile platform for nanomedicine. study introduces an innovative method treat IDD advances integration immunotherapy nanotechnology, offering both clinical benefits new directions future research. These findings hold strong patient outcomes expanding treatment options related diseases.

Language: Английский

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Lipid metabolic disorders and their impact on cartilage endplate and nucleus pulposus function in intervertebral disk degeneration

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: March 10, 2025

Lipid metabolism encompasses the processes of digestion, absorption, synthesis, and degradation fats within biological systems, playing a crucial role in sustaining normal physiological functions. Disorders lipid metabolism, characterized by abnormal blood levels dysregulated fatty acid have emerged as significant contributors to intervertebral disk degeneration (IDD). The pathogenesis IDD is multifaceted, encompassing genetic predispositions, nutritional metabolic factors, mechanical stressors, trauma, inflammatory responses, which collectively facilitate progression IDD. Although precise mechanisms underlying remain incompletely elucidated, there substantial consensus regarding close association between disorders its development. Intervertebral disks are essential for maintaining spinal alignment. Their primary functions encompass shock preservation curvature, facilitation movement, provision stability. elasticity thickness these effectively absorb daily impacts, safeguard spine, uphold natural curvature flexibility, while also creating space nerve roots prevent compression ensure transmission signals. Research indicates that such disturbances may compromise functionality cartilaginous endplates (CEP) nucleus pulposus (NP), thereby facilitating IDD’s onset progression. CEP integral internal material exchange absorption mitigating NP herniation under load conditions. As central component disks, height providing shock-absorbing capabilities; thus, damage critical structures accelerates Furthermore, contribute through including activation endoplasmic reticulum stress pathways, enhancement oxidative levels, induction cellular pyroptosis alongside inhibition autophagy processes—coupled with promotion inflammation-induced fibrosis fibroblast proliferation leading calcification disks. This review delineates intricate interplay IDD; it anticipated advancing our understanding this will pave way more effective preventive measures therapeutic strategies against future research.

Language: Английский

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Integrating bioinformatics and experimental validation to Investigate IRF1 as a novel biomarker for nucleus pulposus cells necroptosis in intervertebral disc degeneration

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 3, 2024

Intervertebral disc degeneration (IDD) is a prevalent spinal disorder and the principal cause of lower back pain (LBP). Diverse forms programmed cell death (PCD) have been identified as key phenotypes disease potential to serve new indicators for diagnosis prognosis IDD. However, mechanism underlying necroptosis in IDD remains unclear. This study aimed identify novel biomarkers that promote nucleus pulposus using bioinformatic analysis experimental validation. We analyzed multiple datasets from Gene Expression Omnibus (GEO) database necroptosis-related differential genes (NRDEGs). Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses were performed, followed by logistic least absolute shrinkage selection operator (LASSO) support vector machine-recursive (SVM) algorithms genes. set enrichment (GSEA) regression used ascertain functions these genes, respectively. then constructed mRNA-miRNA, mRNA-TF, mRNA-drug, functional similarity gene interaction networks seven identified. clinical samples necroptotic model validate our findings. Immunohistochemical staining, RT-qPCR, western blotting results indicated IRF1 may be hub gene. To further elucidate function IRF1, we knockdown overexpression models, which revealed promotes rat cells, increases mitochondrial ROS levels, decreases ATP levels. These findings provide insights into development and, first time, role biomarker treatment

Language: Английский

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