Quercetin as a promising intervention for rat osteoarthritis by decreasing M1‐polarized macrophages via blocking the TRPV1‐mediated P2X7/NLRP3 signaling pathway DOI
W Li, Hebei He, Min Du

et al.

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(4), P. 1990 - 2006

Published: Feb. 19, 2024

Abstract Osteoarthritis (OA) is characterized by an imbalance between M1 and M2 polarized synovial macrophages. Quercetin has shown protective effects against OA altering M1/M2‐polarized macrophages, but the underlying mechanisms remain unclear. In this study, rat chondrocytes were treated with 10 ng/mL of IL‐1β. To create M1‐polarized macrophages in vitro, bone marrow‐derived (rBMDMs) 100 LPS. mimic conditions observed vivo, a co‐culture system was established. ATP release assays, immunofluorescence Fluo‐4 AM staining, Transwell ELISA flow cytometry performed. Male adult Sprague–Dawley (SD) rats used to model. Histological analyses, including H&E, safranin O‐fast green staining Our data showed quercetin‐mediated suppression calcium ion influx release, concurrent downregulation TRPV1 P2X7 Activation abolished on system, overexpression attenuated polarization, migration, inflammation. Either or NLRP3 knockdown IL‐1β‐induced M1/M2 Moreover, reduced suppressive promoting vivo. Collectively, our that quercetin‐induced leads delay progression shifting macrophage polarization from subtypes via modulation P2X7/NLRP3 pathway.

Language: Английский

Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis DOI Creative Commons
Sanjay Basak,

Kota Sri Naga Hridayanka,

Asim K. Duttaroy

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 3, 2024

Bioactives significantly modify and maintain human health. Available data suggest that might play a beneficial role in chronic inflammatory diseases. Although promised, defining their mechanisms opting to weigh benefits limitations is imperative. Detailed by which critical Bioactives, including probiotics prebiotics such as dietary lipids (DHA, EPA, alpha LA), vitamin D, polysaccharides (fructooligosaccharide), polyphenols (curcumin, resveratrol, capsaicin) potentially modulate inflammation bone metabolism limited. Certain bioactive impact the gut microbiota, immune system, pain response via gut-immune-bone axis. This narrative review highlights recent update on mechanistic evidence demonstrated reduce osteoarthritis pathophysiology.

Language: Английский

Citations

9
XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression DOI Creative Commons
Wei Sun,

Zhongyang Lv,

Weitong Li

et al.

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 44, P. 114 - 124

Published: Jan. 1, 2024

Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there still a lack of therapy that can modify OA progression due to complex pathogenic mechanisms. The aim study was explore role and mechanism XJB-5-131 inhibiting chondrocytes ferroptosis alleviate progression. We treated tert-butyl hydroperoxide (TBHP)-induced mouse primary with in vitro. intracellular ferroptotic hallmarks, cartilage anabolic catabolic markers, regulatory genes proteins were detected. Then we established model via destabilization medial meniscus (DMM) surgery. mice intra-articular injection regularly (2 μM, 3 times per week). After 4 8 weeks, performed micro-CT histological examination evaluate protection subjects. RNA sequencing analysis unveil key downstream gene exerting anti-ferroptotic effect OA. significantly suppressed TBHP-induced increases hallmarks (ROS, lipid peroxidation, Fe2+ accumulation), drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored expression suppressors (Gpx4, Fth1). evidently promoted decreased markers. Moreover, inhibited Cox2 Mmp13, Col2a1, Gpx4 Fth1 DMM-induced articular cartilage. Further, identified Pebp1 as potential target by analysis. anti-ferroptosis chondroprotective effects diminished Locostatin, specific antagonist Pebp1. protects from DMM surgery-induced restoring therapeutic drug management

Language: Английский

Citations

9
Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway DOI Creative Commons
Juanjuan Han,

Li-nan Zhan,

Yue Huang

et al.

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

Published: March 1, 2024

Abstract Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process osteoarthritis (OA). Herein, we investigated protective effect moderate mechanical stress on chondrocyte ferroptosis and further revealed internal molecular mechanism. Intra-articular injection sodium iodoacetate (MIA) was conducted to induce rat model OA vivo, meanwhile, interleukin-1 beta (IL-1β) treated chondrocytes vitro. The phenotype analyzed by histology microcomputed tomography, transmission electron microscope immunofluorescence. expression cartilage metabolism-related factors immunohistochemical Western blot. Animal experiments moderate-intensity treadmill exercise could effectively reduce matrix degradation MIA-induced rats. Cell showed 4-h cyclic tensile strain intervention activate Nrf2 inhibit NF-κB signaling pathway, increase Col2a1, GPX4, SLC7A11, decrease MMP13 P53, thereby restraining IL-1β-induced degeneration. Inhibition pathway relieved Meanwhile, overexpression recombinant lentivirus reversed positive CTS chondrocytes. Moderate antioxidant system, p65 regulating GPX4.

Language: Английский

Citations

9
Advancing skeletal health and disease research with single-cell RNA sequencing DOI Creative Commons
Peng Lin, Yibo Gan,

Jian He

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 30, 2024

Abstract Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of underlying pathological processes at cellular and molecular level has hindered development comprehensive treatment options for these disorders. The advent single-cell RNA sequencing (scRNA-seq) technology revolutionized biomedical research by enabling detailed examination diversity. Nevertheless, investigating mechanisms in highly mineralized skeletal tissue poses technical challenges. In this review, we present a streamlined approach to obtaining high-quality single cells from provide an overview existing scRNA-seq technologies employed studies along with practical bioinformatic analysis pipelines. By utilizing methodologies, crucial insights into developmental dynamics, maintenance homeostasis, involved spine, joint, bone, muscle, tendon disorders been uncovered. Specifically focusing on joint diseases degenerative disc disease, osteoarthritis, rheumatoid arthritis using provided novel more nuanced comprehension. These findings paved way discovering therapeutic targets that offer potential benefits patients suffering diverse

Language: Английский

Citations

9
Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption DOI Creative Commons
Peng Ding, Chuan Gao, Jian Zhou

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 14, 2024

Abstract Interactions between osteolineage cells and myeloid play important roles in maintaining skeletal homeostasis. Herein, we find that transfer mitochondria to cells. Impairment of the by deleting MIRO1 leads increased cell commitment toward osteoclastic lineage promotes bone resorption. In detail, impaired mitochondrial from alters glutathione metabolism protects ferroptosis, thus promoting osteoclast activities. Furthermore, is involved regulation glucocorticoid-induced osteoporosis, depletion alleviates progression osteoporosis. These findings reveal an unappreciated mechanism underlying interaction regulate metabolic homeostasis provide insights into osteoporosis progression.

Language: Английский

Citations

9
Ion channels in osteoarthritis: emerging roles and potential targets DOI
Renpeng Zhou, Wenyu Fu,

Dmytro V. Vasylyev

et al.

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(9), P. 545 - 564

Published: Aug. 9, 2024

Language: Английский

Citations

9
Clinical and omics biomarkers in osteoarthritis diagnosis and treatment DOI Creative Commons

Muhai Deng,

Cong Tang,

Li Yin

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 295 - 305

Published: Jan. 1, 2025

Language: Английский

Citations

1
Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis DOI Creative Commons
Yuan Liu, Wacili Da,

Mingjie Xu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract Research on treating knee osteoarthritis (KOA) is becoming more challenging due to a growing number of younger patients being affected. The pathogenesis KOA complex for multifactorial disease affecting the entire joint, with remodeling subchondral bone playing key role in degeneration overlying cartilage. Therefore, this study constructed bipedal postmenopausal mouse model better understand how interplay between and cartilage contributes development. A single-cell atlas osteochondral composite tissue was established. Furthermore, three novel subtypes chondrocytes, including Smoc2 + angiogenic Angptl7 Col1a1 osteogenic were identified femoral condyles mice. In addition, chondrocytes promoted angiogenesis mice by interacting endothelial cells via FGF2-FGFR2 signaling pathway. H-type vessels increased bone, recruiting osteoprogenitor facilitating osteogenesis Sparc osteoblasts have negatively regulated mineralization osteoblastic differentiation, aggravated pathological progression KOA. above findings offered new targets opened up an avenue therapeutic intervention

Language: Английский

Citations

1
JP4-039 protects chondrocytes from ferroptosis to attenuate osteoarthritis progression by promoting Pink1/Parkin-dependent mitophagy DOI Creative Commons

Xie Ya,

Zhongyang Lv,

Weitong Li

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 132 - 144

Published: March 1, 2025

Osteoarthritis (OA) is the most common degenerative joint disease, and its main pathological mechanism articular cartilage degeneration. The purpose of this study was to investigate role mitophagy in pathogenesis chondrocyte ferroptosis OA. expressions related proteins (GPX4, FTH1, COX2) ubiquitin-dependent (PARKIN, PINK1) intact injured areas OA were analyzed. Nitro oxide JP4-039, a mitochondrial targeting antioxidant, has bifunctional mitochondria. Then we evaluated potential protective effect JP4-039 using destabilization medial meniscus (DMM)-induced model, as well tert-butyl hydrogen peroxide (TBHP)-treated primary mouse chondrocytes human explants. concentrations iron lipid peroxidation expression drivers damaged cartilages significantly higher than those cartilage. Pink1/Parkin-dependent decreased area negatively correlated with ferroptosis. Then, toxicity effectiveness are tested determine working concentration. Next, at molecular biological level, found that showed anti-chondrocyte Moreover, it verified on DMM-induced model mice, could delay progression Finally, re-verified vivo vitro inhibit by promoting mitophagy. inhibits delays progression.

Language: Английский

Citations

1
CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications DOI Creative Commons
Zhe Gong, Jinjin Zhu, Junxin Chen

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 28, 2023

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid and upregulation senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 highly expressed in secondary generation chondrocytes its deficiency can alleviate FASN related senescent phenotypes osteoarthritis progression. impedes proteasome-mediated degradation inhibiting acetylation-mediated ubiquitination. Meanwhile, induces RanBP2-mediated SUMOylation enhances protein stability. CircRREB1-FASN axis inhibits FGF18 FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection adenovirus-CircRreb1 reverses the protective effects CircRreb1 mice. Further therapeutic interventions could have beneficial identifying as potential prognostic target for OA.

Language: Английский

Citations

23