ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting p21-Positive Senescent Chondrocytes via IL-6R/JAK2 Inhibition to Alleviate Osteoarthritis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Hyperbaric oxygen therapy for knee osteoarthritis: treatment mechanism, potential advantages, and limitations.Medical gas research · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Enolase 2-mediated lactylation-dependent disruption of the GNL3-MDM2-p53 axis in age-related osteoarthritis.Cellular & molecular biology letters · 2026Article
- Dihydroxyacetone nanoparticles ameliorate osteoarthritis via P21-mediated regulation of chondrocyte repair.Journal of nanobiotechnology · 2026Article
- p21 Knockdown as a Therapeutic Strategy for Focal Cartilage Injury Repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Association between the Framingham steatosis index and osteoarthritis: evidence of mediation by phenotypic age.Scientific reports · 2026Article
- Injectable microgels carrying engineered biomimetic nanoparticles for osteoarthritis therapy via dual-targeted senescent chondrocyte clearance and endogenous repair promotion.Bioactive materials · 2026Article
- The emerging role of histone acetylation in rheumatic diseases: unraveling mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Inflammaging and immunosenescence-driven remodeling of the immune microenvironment in osteoarthritis: mechanisms, immune regulation and immune reprogramming.Frontiers in immunology · 2026Review
- Abnormal mechanical load aggravates subchondral bone remodeling and uneven tibial plateau settlement in knee osteoarthritis via activation of osteoblast Piezo1-Ca²⁺-JAK2/STAT3 signaling.International journal of biological sciences · 2026Article
- The central role of IL-6 in the differential effects of GLP-1 receptor agonists and metformin across multiple health conditions.Frontiers in immunology · 2026Review
- Pathogenesis of Osteoarthritis: Mechanisms of Action of Disulfidptosis and Targeted Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Association of inflammatory, genetic, and epigenetic markers with Kellgren-Lawrence grading in post-traumatic osteoarthritis of knee: A protocol.World journal of experimental medicine · 2025Article
- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
- Multi-omics and experimental validation studies reveal key biomarkers of cellular senescence in diabetic retinopathy.Diabetology & metabolic syndrome · 2025Article
- Targeting p21-Positive Senescent Chondrocytes via IL-6R/JAK2 Inhibition to Alleviate Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Osteoarthritis (OA) is an age-related degenerative joint disease, prominently influenced by the pro-inflammatory cytokine interleukin-6 (IL-6). Although elevated IL-6 levels in joint fluid are well-documented, the uneven cartilage degeneration observed in knee OA patients suggests additional underlying mechanisms. This study investigates the role of interleukin-6 receptor (IL-6R) in mediating IL-6 signaling and its contribution to OA progression. Here, significantly elevated IL-6R expression is identified in degenerated cartilage of OA patients. Further, in vivo experiments reveal that intra-articular injection of recombinant IL-6R protein or activation of gp130 (Y757F mutation) accelerates OA progression. Conversely, knockout of IL-6R or JAK2, as well as treatment with a JAK inhibitor, alleviates OA symptoms. Mechanistically, chondrocytes derived from degenerative cartilage exhibit impaired nuclear localization of SOX9, a key regulator of cartilage homeostasis. JAK inhibition stabilizes SIRT1, reduces SOX9 acetylation, and thereby facilitates SOX9 nuclear localization, promoting cartilage repair. Additionally, the JAK inhibitor-induced apoptosis in p21-positive senescent cells, and their targeted clearance successfully alleviates OA in p21-3MR mice. In conclusion, these findings reveal a novel mechanism by which inhibiting the IL-6R/JAK2 pathway can alleviate OA. Furthermore, this study proposes targeting p21-positive senescent cells as a new therapeutic strategy for OA.
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