Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)
Published: Jan. 31, 2025
Language: Английский
Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 46, P. 65 - 78
Published: May 1, 2024
Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, mechanisms responsible for iron ion accumulation tissues and mechanism that regulate homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as primary cellular gate, playing pivotal role controlling intracellular levels, however its involvement IDD pathogenesis underlying remains obscure. Firstly, mice model was established to determine metabolism proteins changes during progression. Then CEP chondrocytes were isolated treated TBHP or pro-inflammatory cytokines mimic pathological environment, western blotting, immunofluorescence assay tissue staining employed explore mechanisms. Lastly, TfR1 siRNA Feristatin II of examined using micro-CT immunohistochemical analysis. We found characterized by oxidative stress cytokines, could enhance influx upregulating TFR1 expression HIF-2α dependent manner. Excessive not only induces ferroptosis exacerbates stress, but also triggers innate immune response mediated c-GAS/STING, promoting mitochondrial damage release mtDNA. The inhibition STING through reduction mtDNA replication ethidium bromide alleviated induced overload. Our study systemically explored mechanisms, implying targeting maintain balanced offer promising therapeutic approach management. demonstrated close link between dysfunction IDD, indicated may be novel strategy IDD.
Language: Английский
Citations
7
Cells, Journal Year: 2022, Volume and Issue: 11(21), P. 3508 - 3508
Published: Nov. 5, 2022
Intervertebral disc degeneration (IVDD) is a common pathological condition responsible for lower back pain, which can significantly increase economic and social burdens. Although considerable efforts have been made to identify potential mechanisms of degeneration, the treatment IVDD not satisfactory. Ferroptosis, recently reported form regulated cell death (RCD), characterized by iron-dependent lipid peroxidation has demonstrated be variety degenerative diseases. Accumulating evidence suggests that ferroptosis implicated in decreasing viability increasing extracellular matrix degradation nucleus pulposus cells, annulus fibrosus or endplate chondrocytes. In this review, we summarize literature regarding intervertebral cells discuss its molecular pathways biomarkers treating IVDD. Importantly, verified as promising therapeutic target
Language: Английский
Citations
28
Bioactive Materials, Journal Year: 2022, Volume and Issue: 23, P. 551 - 562
Published: Dec. 12, 2022
Intervertebral disc (IVD) degeneration is a leading cause of back pain and precursor to more severe conditions, including herniation spinal stenosis. While traditional growth factor therapies (e.g., TGFβ) are effective at transiently reversing degenerated by stimulation matrix synthesis, it increasingly accepted that bioscaffolds required for sustained, complete IVD regeneration. Current scaffolds metal/polymer composites, non-mammalian biopolymers) can be improved in one or regeneration demands: biodegradability, noninvasive injection, recapitulated healthy biomechanics, predictable crosslinking, repair induction. To meet these demands, tetrazine-norbornene bioorthogonal ligation was combined with gelatin create an injectable hydrogel (BIOGEL). The liquid precursors remain free-flowing across wide range temperatures crosslink into robust after 5-10 min, allowing human operator easily inject the therapeutic constructs IVD. Moreover, BIOGEL encapsulation TGFβ potentiated histological tissue architecture synthesis) functional recovery high water retention promoting synthesis reduced pain) vivo rat degeneration/nucleotomy model. This procedure readily integrates existing nucleotomy procedures, indicating clinical adoption should proceed minimal difficulty. Since crosslinking essentially non-reactive towards biomolecules, our developed material platform extended other payloads degenerative injuries.
Language: Английский
Citations
24
Cells, Journal Year: 2023, Volume and Issue: 12(17), P. 2161 - 2161
Published: Aug. 28, 2023
Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of degenerated IVD but typically have incomplete resolutions because their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as mainstream research objective by World Health Organization and was consequently studied various groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, anti-pyroptotic effects promote extracellular component production, well differentiation into cells themselves. Hence, ultimate goal MSC to recover regenerate matrix IVDs. Notably, in addition implantation, healthy nucleus pulposus (NP) (NPCs) implanted NP, which currently undergoing clinical trials. NPC-derived exosomes investigated ability differentiate from NPC-like phenotypes. A stable economical source may include allogeneic bank cells. multiple alternative therapeutic options should be considered if refined protocol established. In this study, we comprehensively reviewed molecules, scaffolds, environmental factors that facilitate therapies IDD.
Language: Английский
Citations
15
Aging Cell, Journal Year: 2024, Volume and Issue: 23(9)
Published: May 23, 2024
The nucleus pulposus is in a hypoxic environment the human body, and when intervertebral disc degeneration (IVDD) occurs, disrupted. Nucleus cell (NPC) ferroptosis one of causes IVDD. N6-methyladenosine (m6A) its reader protein YTHDF1 regulate cellular activities by affecting RNA metabolism. However, regulation NPCs m6A-modified RNAs under conditions has not been as well studied. In this study, through vitro vivo experiments, we explored underlying mechanism HIF-1α regulating NPCs. results indicated that overexpression or suppressed NPC ferroptosis; conversely, knockdown increased levels Luciferase reporter assays chromatin immunoprecipitation demonstrated regulated transcription directly binding to promoter region. Polysome profiling showed promoted translation SLC7A11 consequently expression anti-ferroptosis GPX4 mRNA. conclusion, HIF-1α-induced reduces delays IVDD promoting m6A-dependent manner.
Language: Английский
Citations
6
Materials Today Bio, Journal Year: 2024, Volume and Issue: 26, P. 101081 - 101081
Published: May 3, 2024
The degeneration of intervertebral discs is strongly associated with the occurrence pyroptosis in nucleus pulposus (NP) cells. This characterized by abnormal metabolism fatty acids degenerative pathological state, which further exacerbated inflammatory microenvironment and degradation extracellular matrix. In order to address this issue, we have developed a fibrin hydrogel complex (FG@PEV). intricate formulation amalgamates beneficial attributes platelet extravasation vesicles, contributing tissue repair regeneration. Furthermore, showcases exceptional stability, gradual-release capabilities, high degree biocompatibility. substantiate biological significance FG@PEV disc (IVDD), conducted comprehensive investigation into its potential mechanism action through integration RNA-seq sequencing metabolomics analysis. these findings were subsequently validated experimentation both vivo vitro models. experimental results revealed that intervention possesses capability reshape within disc. It also addresses irregularities acid cells, consequently hindering cellular slowing down regulation matrix synthesis degradation. As result, injectable gel system represents promising innovative therapeutic approach for mitigating degeneration.
Language: Английский
Citations
5
The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(7)
Published: June 23, 2022
Abstract Intervertebral disc (IVD) degeneration (IVDD) is closely linked to degenerative spinal disease, resulting in disability, poor quality of life, and financial burden. Apoptosis nucleus pulposus (NP) cells (NPCs) a key pathological basis IVDD. Periostin (POSTN), an extracellular matrix protein, expressed many tissues, whereas its abnormal expression associated with The conventional Wnt/β‐catenin pathway also involved IVDD contributes NPCs apoptosis. However, research on the mechanisms POSTN lacking. This study investigated relationship between β‐catenin degenerated IVDs. We detected POSTN, β‐catenin, cleaved‐caspase‐3 (C‐caspase3) non‐degenerated IVD tissues different grades ( n = 8) using RT‐qPCR, immunohistochemical staining, western blotting analysis. Next, we explored effects recombinant periostin (rPOSTN) isoquercitrin (Iso), inhibitor pathway, Finally, inhibited vivo anti‐apoptotic effect. C‐caspase3 severe IVDs was significantly higher than that mild These findings were confirmed rat cell‐based models. When treated rPOSTN, activity cell apoptosis time‐ dose‐dependent. rPOSTN‐induced decreased after iso‐induced inhibition pathway. reduced but restored by rPOSTN re‐addition. Lastly, ameliorated puncture‐induced vivo. Overall, our demonstrated promotes aggravates activating
Language: Английский
Citations
22
International Immunopharmacology, Journal Year: 2023, Volume and Issue: 121, P. 110400 - 110400
Published: June 7, 2023
Language: Английский
Citations
12
Cell Proliferation, Journal Year: 2023, Volume and Issue: 57(2)
Published: Sept. 11, 2023
Abstract Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal degenerative disorder worldwide, and ~40% of chronic low back pain cases are associated with IDD. Although the pathogenesis IDD remains unclear, reduction in nucleus pulposus cells (NPCs) degradation extracellular matrix (ECM) critical factors contributing to Notochordal (NCs), derived from notochord, which rapidly degrades after birth eventually replaced by NPCs, play crucial role maintaining ECM homeostasis preventing NPCs apoptosis. Current treatments for only provide symptomatic relief, while lacking ability inhibit or reverse its progression. However, NCs their secretions possess anti‐inflammatory properties promote proliferation, leading formation. Therefore, recent years, therapy targeting underlying cause has emerged as novel treatment strategy. This article provides comprehensive review latest research progress on IDD, covering biological characteristics, specific markers, possible mechanisms involved therapeutic effects. It also highlights significant future directions this field facilitate further exploration development new therapies based strategies.
Language: Английский
Citations
12
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116001 - 116001
Published: Dec. 20, 2023
Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate heavy burden on society. IVDD characterized by decrease in nucleus pulposus cells (NPCs) endogenous mesenchymal stem (MSCs), degradation the extracellular matrix, macrophage infiltration, blood vessel nerve ingrowth. To date, therapeutic approaches regarding mainly include conservative treatment surgical intervention. However, both only relieve symptoms rather than stop or revert progression IVDD, since pathogenesis not yet clear. Pyroptosis, Caspase family dependence conducted Gasdermin family, newly discovered mode programmed cell death. Pyroptosis has been observed NPCs, annulus fibrosus (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial neurons may contribute IVDD. MSCs are kind pluripotent that be found almost all tissues. have strong ability secrete vesicles (EVs), contain exosomes, microvesicles apoptotic bodies. EVs derived from play an important role pyroptosis regulation could beneficial for alleviating This review focuses clarifying improve MSCs.
Language: Английский
Citations
12