ArticleNature communications2025
Denosumab attenuates knee osteoarthritis progression by inhibiting synovial inflammation via the RANK/TRAF6/FSTL1 signalling.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Decreased incidence of shoulder arthroplasty in patients prescribed anti-resorptive therapy for osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- From Joint Loading to Osteoarthritis: A Multiscale Review of Knee Mechanobiology and Digital Modelling.International journal of molecular sciences · 2026Review
- Camouflage Protein-Engineered Extracellular Vesicles Alleviate TMJ-OA by Hijacking Caspase-1 to Suppress Pyroptosis.Journal of extracellular vesicles · 2026Article
- Repurposing Denosumab for Knee Osteoarthritis: A Real-World Signal That Now Needs a Trial.International journal of rheumatic diseases · 2026Article
- Osteoclast Heterogeneity in Osteoarthritis: From Single-Cell Microenvironments to Program-Specific Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Bridging the gap in OA therapeutics: Bioengineered strategies to target osteoclast-chondrocyte crosstalk.Bioengineering & translational medicine · 2026Review
- Synovial transcriptional clusters link cartilage degeneration to cell-type-specific gene expression in knee osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Integrative analysis of single-cell and bulk RNA sequencing data using machine learning identifies PTGDS as a key subsynovial fibroblast gene in osteoarthritis.Journal of molecular histology · 2026Article
- Denosumab targets synovial inflammation to attenuate knee OA.Nature reviews. Rheumatology · 2026Article
- Synovial immune control failure in osteoarthritis: from maintenance of tissue homeostasis to inflammatory niche formation.Frontiers in immunology · 2026Review
- Electroacupuncture attenuates synovitis in knee osteoarthritis and is associated with modulation of the protein S-TAM (Axl/MerTK)-Rac1 signaling axis.Frontiers in immunology · 2026Article
- Denosumab in osteoarthritis: from mechanism to clinical translation.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Synovitis has recently been shown to be a critical early stage in development of osteoarthritis (OA), and inhibiting synovitis significantly alleviates OA symptoms. Denosumab, a monoclonal antibody targeting RANKL, previously developed for osteoporosis. Here, we report the effect of denosumab on fibroblast-like synoviocytes (FLSs), attenuating synovitis and consequently OA progression. We first demonstrate that RANKL is highly expressed in the knee synovium of OA mice, as well as in patients. Next, we show that denosumab, injected systemically, accumulates in the synovium and effectively reduces synovitis through RANK/TRAF6/FSTL1 signalling in post-traumatic, inflammatory, and aged OA murine models and a beagle dog OA model, delaying OA progression. Finally, a single-arm clinical trial with primary endpoints of VAS and OKS scores, and secondary endpoints of WOMAC score and adverse events rate, shows that denosumab alleviates synovitis and pain, improving joint function in knee OA patients. These findings provide a translational basis for using denosumab to treat knee OA in the clinic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.