TRPC1 links calcium signaling to cellular senescence in the protection against post-traumatic osteoarthritis DOI Creative Commons

Meike Sambale,

Starlee Lively, Osvaldo Espin‐Garcia

и другие.

JCI Insight, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

Transient receptor potential channel 1 (TRPC1) is a widely expressed mechanosensitive ion located within the endoplasmic reticulum membrane, crucial for refilling depleted internal calcium stores during activation of calcium-dependent signaling pathways. Here, we demonstrate that TRPC1 activity protective cartilage homeostasis in prevention cellular senescence associated breakdown mechanical and inflammatory challenge. We reveal loss with early stages osteoarthritis (OA) plays non-redundant role chondrocytes. Trpc1-/- mice subjected to destabilization medial meniscus induced OA developed more severe phenotype than wild type controls. During development, displayed an increased chondrocyte survival rate, however remaining cells features including p16INK4a expression decreased Sox9. RNA sequencing identified differentially genes related cell number, apoptosis extracellular matrix organization. Trpc1-/-chondrocytes exhibited accelerated dedifferentiation, while demonstrating susceptibility senescence. Targeting mechanism Trpc1 may be promising therapeutic strategy prevention.

Язык: Английский

A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression DOI Creative Commons
Qiuyang Wang, Kai Feng,

Guangsheng Wan

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 16, 2025

RNA interference (RNAi) and oxidative stress inhibition therapeutic strategies have been extensively utilized in the treatment of osteoarthritis (OA), most prevalent degenerative joint disease. However, synergistic effects these approaches on attenuating OA progression remain largely unexplored. In this study, matrix metalloproteinase-13 siRNA (siMMP-13) was incorporated onto polyethylenimine (PEI)-polyethylene glycol (PEG) modified Fe3O4 nanoparticles, forming a nucleic acid nanocarrier termed si-Fe NPs. Subsequently, poly(vinyl alcohol) (PVA) crosslinked phenylboronic (PBA)-modified hyaluronic (HA) hydrogel (HPP) used to encapsulate NPs, resulting bifunctional (si-Fe-HPP) with reactive oxygen species (ROS)-responsive RNAi properties. Studies vitro demonstrated that si-Fe-HPP exhibited excellent biocompatibility, anti-inflammatory prolonged stable retention time knee joint. Intra-articular injection significantly attenuated cartilage degradation mice destabilization medial meniscus (DMM)-induced OA. The not only notably alleviated synovitis, osteophyte formation subchondral bone sclerosis, but also markedly improved physical activity reduced pain DMM-induced mice. This study reveals si-Fe-HPP, its ROS-responsive abilities, can protect chondrocytes attenuate progression, providing novel insights directions for development materials treatment.

Язык: Английский

Процитировано

4
Engineered MSC‐sEVs as a Versatile Nanoplatform for Enhanced Osteoarthritis Treatment via Targeted Elimination of Senescent Chondrocytes and Maintenance of Cartilage Matrix Metabolic Homeostasis DOI Creative Commons
Kai Feng, Jiashuo Liu,

Liangzhi Gong

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 4, 2025

Abstract Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro‐inflammatory factors. Mesenchymal stem cells‐derived small extracellular vesicles (MSC‐sEVs) have shown anti‐inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on required to facilitate translation MSC‐sEVs treatment. In this study, versatile engineered are developed targetedly clear and maintain metabolic homeostasis. Specifically, loaded with siRNA mouse double minute 2 homologue (siMDM2) modified cartilage‐targeting peptide WYRGRL‐PEG 2K ‐DSPE (WPD), named WPD‐sEVs siMDM2 . The results demonstrate modification improves cellular uptake chondrocytes, thus antiaging effects. Importantly, multifunctional enhances penetration extends joint retention time MSC‐sEVs. both post‐traumatic mice naturally aged mice, more effectively eliminates maintained matrix By using P53 phosphorylation inhibitor, essential role MDM2‐P53 pathway function verified. ex vivo cultured human explants, it confirmed that alleviates phenotype. Altogether, findings suggest promising translational potential for

Язык: Английский

Процитировано

2
The intersection of aging and estrogen in osteoarthritis DOI Creative Commons
Aysegul Atasoy‐Zeybek,

Kelly K. Showel,

Christopher V. Nagelli

и другие.

npj Women s Health, Год журнала: 2025, Номер 3(1)

Опубликована: Фев. 25, 2025

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, inflammation, and pain. While multiple factors contribute to OA development, age sex are primary risk factors, particularly affecting postmenopausal women. The dramatic increase in after menopause suggests estrogen deficiency accelerates progression. This review explores the molecular mechanisms connecting aging focusing on key genes pathways identified through RNA sequencing.

Язык: Английский

Процитировано

2
Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk DOI
Nicole E. Kramer, Seyoun Byun, Philip Coryell

и другие.

Cell Genomics, Год журнала: 2025, Номер 5(1), С. 100738 - 100738

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Epidemiological trends and characteristics of osteoarthritis in China during 1990–2021 DOI Creative Commons
Sheng Chen, Mingjue Chen, Chao Chen

и другие.

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 51, С. 218 - 226

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
CPP-calcification of articular cartilage is associated with elevated cytokine levels in synovial fluid DOI Creative Commons
Sina Stücker,

Franziska Koßlowksi,

Adrian Buchholz

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 19, 2025

Background Calcification of articular tissues is commonly observed in later osteoarthritis (OA) stages and can be caused by basic calcium phosphate (BCP) or pyrophosphate (CPP) crystals. Calcification, particularly CPP deposition, has recently been associated with inflammation cellular senescence. Investigating this association, we analyzed the concentration various inflammatory mediators synovial fluid membrane OA patients relation to calcification different crystal types. Methods Synovial was collected from during joint replacement surgery. Cytokine concentrations were measured using magnetic bead-based multiplex assay Luminex® technology. Radiographs used determine grade knee involved types identified via Raman spectroscopy. Results radiological showed elevated levels multiple cytokines (IL-10, IL-15, IL-1ra, GM-CSF), chemokines (IL-8, MCP-1, MIP-1b) growth factors (PDGF-AB/BB, VEGF). Crystal differentiation revealed higher IL-10, GM-CSF, PDGF-AB/BB MIP-1b CPP- compared BCP-calcified cartilage. Conclusion We show an cytokine profile that may linked depositison

Язык: Английский

Процитировано

1
Pain Relief, Functional Recovery, and Chondroprotective Effects of Angelica gigas Nakai in Osteoarthritis Due to Its Anti-Inflammatory Property: An In Vitro and In Vivo Study DOI Open Access
Hee-Geun Jo,

Chae Yun Baek,

Yeseul Hwang

и другие.

Nutrients, Год журнала: 2024, Номер 16(15), С. 2435 - 2435

Опубликована: Июль 26, 2024

Osteoarthritis (OA), characterized by chronic pain and joint degradation, is a progressive disease primarily induced age-related systemic inflammation.

Язык: Английский

Процитировано

4
Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk DOI Creative Commons
Nicole E. Kramer, Seyoun Byun, Philip Coryell

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 5, 2024

Osteoarthritis (OA) poses a significant healthcare burden with limited treatment options. While genome-wide association studies (GWAS) have identified over 100 OA-associated loci, translating these findings into therapeutic targets remains challenging. Integrating expression quantitative trait loci (eQTL), 3D chromatin structure, and other genomic approaches OA GWAS data offers promising approach to elucidate disease mechanisms; however, comprehensive eQTL maps in OA-relevant tissues conditions remain scarce. We mapped gene expression, accessibility, structure primary human articular chondrocytes both resting OA-mimicking conditions. thousands of differentially expressed genes, including those associated differences sex age. RNA-seq from 101 donors across two uncovered 3782 unique eGenes, 420 that exhibited strong condition-specific effects. Colocalization signals revealed 13 putative risk 10 which not been previously identified. Chromatin accessibility provided insights the mechanisms conditional specificity variants. Our shed light on pathogenesis highlight potential for development.

Язык: Английский

Процитировано

3
Targeting p38 MAPK: A potential bridge between ER stress and age-related bone loss DOI
Meng Yin, Xin Zheng, Liang Shi

и другие.

Cellular Signalling, Год журнала: 2024, Номер 127, С. 111549 - 111549

Опубликована: Дек. 7, 2024

Язык: Английский

Процитировано

3
Polyunsaturated fatty acids suppress PIEZO ion channel mechanotransduction in articular chondrocytes DOI Open Access

Gabrielle K. Marushack,

Alireza Savadipour, Ruhang Tang

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(1)

Опубликована: Янв. 9, 2025

Abstract Osteoarthritis (OA) is characterized by articular cartilage degeneration, leading to pain and loss of joint function. Recent studies have demonstrated that omega‐3 (ω3) polyunsaturated fatty acid (PUFA) supplementation can decrease injury‐induced OA progression in mice fed a high‐fat diet. Furthermore, PUFAs been shown influence the mechanical properties chondrocyte membranes, suggesting alterations mechanosensitive ion channel signaling could contribute mechanism which ω3 decreased pathogenesis. Here, we hypothesized may alter through PIEZO1 (activated changes membrane tension) TRPV4 physiologic mechano‐osmotic signals), as these cation channels progression. Our results reduced sensitivity single‐cell compression pharmacologic agonists TRPV4, with having most significant effects overall. We also found ω6 PUFA linoleic (LA) altered biophysical chondrocytes, evidenced increased intracellular lipid droplet formation more rapid rupture response hypo‐osmotic shock, LA increases susceptibility damage. findings underscore differential impacts specific on provide important considerations development nutritional interventions prevent or treat OA.

Язык: Английский

Процитировано

0