Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies DOI Creative Commons
Zijun Zhao, Yining Wang, Zairan Wang

и другие.

Immunity Inflammation and Disease, Год журнала: 2024, Номер 12(11)

Опубликована: Ноя. 1, 2024

ABSTRACT Background Intervertebral disc degeneration (IDD) is a major cause for low back pain. Studies showed the association between senescence and degenerative diseases. Cell can promote occurrence development of diseases through multiple mechanisms including inflammatory stress, oxidative stress nutritional deprivation. The roles senescence‐associated genes (SAGs) remains unknown in IDD. Methods Four differently expressed SAGs were identified as hub using “limma“ package R. We then calculated immune infiltration IDD patients, investigated relation infiltration. Enrichment analysis was performed to explore functions Nomogram LASSO model based on constructed predict risk severe (SD) patients. Subsequently, single cell conducted describe expression pattern intervertebral tissue. Results ASPH, CCND1, IGFBP3 SGK1 SAGs. Further demonstrated that might mediate by regulating pathways. four good performance predicting SD. Single revealed CCND1 mainly nucleus pulposus cells, while epithelial cells. Eleven candidate drugs targeting SAGS predicted patients Comparative Toxicogenomics Database (CDT). PCR immunohistochemical levels higher SD than MD (mild degeneration) Conclusions comprehensive IDD, which their Based SAGs, we established predictive explored potential drugs. These findings provide new understandings SAG mechanism promising therapeutic strategies

Язык: Английский

Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles DOI Creative Commons
Shanfeng Chen,

Yiming Dou,

Yiming Zhang

и другие.

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 50, С. 44 - 55

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
From Embryogenesis to Senescence: The Role of Mammary Gland Physiology in Breast Cancer Risk DOI Open Access

Jaida C. Lue,

Derek C. Radisky

Cancers, Год журнала: 2025, Номер 17(5), С. 787 - 787

Опубликована: Фев. 25, 2025

The mammary gland undergoes significant changes throughout a woman's life; from embryonic development to transformations after breastfeeding and during aging. These processes, while essential for normal breast physiology, can increase cancer risk when disrupted. This review explores three critical stages: development; postlactational involution; age-related lobular involution (ARLI). We highlight key signaling pathways-Wnt, FGF, SHH, Notch, EGFR, BMP-that guide discuss how their dysregulation contribute abnormal growth. For involution, we examine the two-phase process of cell death tissue remodeling, showing disruptions this period, particularly postpartum, may foster tumor-promoting environment. also delve into ARLI role cellular senescence in aging gland, focusing on senescence-associated secretory phenotype (SASP) its impact inflammation remodeling. Understanding these processes provides new opportunities prevention treatment strategies.

Язык: Английский

Процитировано

1
Sequential Targeted Enzyme‐Instructed Self‐Assembly Supramolecular Nanofibers to Attenuate Intervertebral Disc Degeneration DOI Open Access
Yang Liu, Xun Sun,

Lianlei Wang

и другие.

Advanced Materials, Год журнала: 2024, Номер 36(41)

Опубликована: Сен. 2, 2024

Abstract As an age‐related disease, intervertebral disc degeneration is closely related to inflammation and aging. Inflammatory cytokines cellular senescence collectively contribute the degradation of disc. Blocking this synergy reduces extracellular matrix damage caused by In study, drug‐loaded nanofibers with sequential targeting functions are constructed through intelligent response, hydrophilicity, in situ self‐assembly empowerment flurbiprofen. The peptide precursor responds cleavage overexpressed MMP‐2 degenerative microenvironment (intracellular extracellular), resulting formation self‐assembled that enable on‐demand release flurbiprofen COX‐2 response. vitro, Comp. 1 (Flurbiprofen‐GFFYPLGLAGEEEERGD) expression inflammation‐related genes proteins polarization M1 macrophages competitively inhibiting increases COL‐2 aggrecan. Additionally, it can reduce Senescence‐Associated Secretory Phenotype DNA aged nucleus pulposus cells promote recovery proliferation cell cycle. vivo, delay preventing accumulation senescent cells. Therefore, sequentially targeted blocking synergistic effect inflammatory senescence.

Язык: Английский

Процитировано

4
PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription DOI Creative Commons
Cheng Yu, Jianjun Li,

Wenhao Kuang

и другие.

Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)

Опубликована: Окт. 21, 2024

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses considerable burden society. However, the molecular mechanisms underlying IVDD remain be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, inflammatory responses in various diseases. Despite these regulatory functions, mechanism of action PRDM1 remains unexplored. In this study, we investigated role progression. The expression nucleus pulposus (NP) tissues NP cells (NPCs) was assessed using western blotting, immunohistochemistry, immunofluorescence. effects on progression were vitro vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, dual-luciferase reporter assays performed confirm that triggered CASP1 transcription. Our study demonstrated for first time substantially upregulated degenerated NPCs. overexpression promoted NPCs pyroptosis by inhibiting mitophagy exacerbating progression, whereas silencing exerted opposite effect. Furthermore, activated transcription, thereby promoting vitro. Notably, reversed To best our knowledge, demonstrate inhibits repressing which may promising new therapeutic target IVDD.

Язык: Английский

Процитировано

4
Research progress on intervertebral disc repair strategies and mechanisms based on hydrogel DOI

Zekun Hua,

Yuyue Zhao, Meng Zhang

и другие.

Journal of Biomaterials Applications, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Intervertebral disc degeneration (IDD) arises from a complex interplay of genetic, environmental, and age-related factors, culminating in spectrum low back pain (LBP) disorders that exert significant societal economic impact. The present therapeutic landscape for IDD poses formidable clinical hurdles, necessitating the exploration innovative treatment modalities. hydrogel, as biomaterial, exhibits superior biocompatibility compared to other biomaterials such bioceramics bio-metal materials. It also demonstrates mechanical properties closer those natural intervertebral discs (IVDs) favorable biodegradability conducive IVD regeneration. Therefore, it has emerged promising candidate material field regenerative medicine tissue engineering treating IDD. Hydrogels have made strides treatment. Particularly, injectable hydrogels not only provide support but enable controlled release bioactive molecules, playing crucial role mitigating inflammation promoting extracellular matrix (ECM) Furthermore, ability achieve minimally invasive implantation helps minimize damage. This article initially provides concise exposition structure function IVD, progression IDD, delineates extant interventions Subsequently, categorizes hydrogels, encapsulates recent advancements cellular therapies, delves into mechanisms through which foster Ultimately, deliberates on prospects challenges attendant hydrogel therapy

Язык: Английский

Процитировано

0
Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases DOI Open Access
Motomichi Fujita,

Manabu Sasada,

Takuya Iyoda

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6591 - 6591

Опубликована: Июнь 15, 2024

Senescence is a physiological and pathological cellular program triggered by various types of stress. Senescent cells exhibit multiple characteristic changes. Among them, the flattened enlarged morphology exhibited in senescent observed regardless stimuli causing senescence. Several studies have provided important insights into pro-adhesive properties senescence, suggesting that cell adhesion to extracellular matrix (ECM), which involved morphological changes, may play pivotal roles Matricellular proteins, group structurally unrelated ECM molecules are secreted environment, unique ability control binding receptors, including integrins. Recent reports certified matricellular proteins closely Through this biological function, thought pathogenesis age-related diseases, fibrosis, osteoarthritis, intervertebral disc degeneration, atherosclerosis, cancer. This review outlines recent on role inducing We highlight integrin-mediated signaling senescence provide new therapeutic options for diseases targeting

Язык: Английский

Процитировано

3
Unveiling the role of CXCL8/CXCR2 in intervertebral disc degeneration: A path to promising therapeutic strategies DOI Creative Commons
Pengfei Xue,

Long Lv,

Lei Liu

и другие.

Journal of Orthopaedic Translation, Год журнала: 2024, Номер 49, С. 119 - 134

Опубликована: Окт. 9, 2024

Язык: Английский

Процитировано

3
Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration DOI

Jiawen Zhan,

Yongzhi Cui, Ping Zhang

и другие.

Advanced Healthcare Materials, Год журнала: 2024, Номер 14(2)

Опубликована: Ноя. 18, 2024

Abstract Cartilage endplate cell (CEPC) and nucleus pulposus (NPC) inflammation are critical factors that contribute to intervertebral disc degeneration (IVDD). Recent evidence indicated iron ion influx, reactive oxygen species (ROS), the cGAS‐STING pathway involved in CEPC inflammatory degeneration. Moreover, cytokines produced by degenerating CEPCs lactic acid accumulation within microenvironment significantly NPC inflammation. Consequently, simultaneous alleviation of correction acidic anticipated reverse IVDD. Herein, CEPC‐targeted engineered exosomes loaded with salvianolic A incorporated into a CaCO 3 /chitosan hydrogel, forming composite gel, CAP‐sEXOs@Gel. Notably, CAP‐sEXOs@Gel shows long local retention, realizes slow release CAP‐sEXOs specific uptake CEPCs. After CEPCs, reduce intracellular ROS inhibiting hypoxia‐inducible factor‐2α (HIF‐2α)/TfR1 expression. Iron influx inhibition maintenance normal mitochondrial function reduced mtDNA leakage, suppresing pathway. Additionally, component neutralizes H + , thereby alleviating Collectively, this novel hydrogel demonstrates ability concurrently inhibit inflammation, presenting promising therapeutic approach for

Язык: Английский

Процитировано

3
mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes DOI Open Access
Dario Troise,

Silvia Mercuri,

Barbara Infante

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8676 - 8676

Опубликована: Авг. 8, 2024

The aging process contributes significantly to the onset of chronic diseases, which are primary causes global mortality, morbidity, and healthcare costs. Numerous studies have shown that removal senescent cells from tissues extends lifespan reduces occurrence age-related diseases. Consequently, there is growing momentum in development drugs targeting these cells. Among them, mTOR SGLT-2 inhibitors garnered attention due their diverse effects: regulate cellular growth, metabolism, immune responses, while glucose reabsorption kidneys, resulting various beneficial metabolic effects. Importantly, may act synergistically by influencing senescence processes pathways. Although direct on combined effects inhibition limited, this review aims highlight potential synergistic benefits senescence.

Язык: Английский

Процитировано

2
Meteorin-like protein alleviates intervertebral disc degeneration by suppressing lipid accumulation in nucleus pulposus cells via PPARα-CPT1A activation DOI

Zhengqi Huang,

Ming Shi, Chao Zhang

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1871(3), С. 167635 - 167635

Опубликована: Дек. 18, 2024

Язык: Английский

Процитировано

1