ArticleArthritis research & therapy2022
Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system.
Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 39 citations in OpenAlex.
- Translating mechanobiology in osteoarthritis to biomaterial-informed therapeutic strategies.Mechanobiology in medicine · 2026Review
- Multi-Tissue Crosstalk Regulating Meniscus Healing Under Inflammation and Physiological Loading.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular senescence links muscle atrophy and posttraumatic osteoarthritis after ACL injury.Function (Oxford, England) · 2026Article
- Advances in heterogeneity and classification of osteoarthritis.Bone research · 2026Review
- The Effect of Retrograde Intramedullary Nail Entry at the Metacarpal Head on Metacarpophalangeal Joint Contact Mechanics.Journal of hand surgery global online · 2026Article
- Photobiomodulation outperforms ultrasound in reducing IL-1APL bioengineering · 2026Article
- Early Unloading After ACL Rupture and Prior to Surgical Restabilization in Mice Slows Post-Traumatic Osteoarthritis Progression.Cartilage · 2026Article
- The association between life's crucial 9 and osteoarthritis in US adults: the mediating role of central adiposity.Nutrition & metabolism · 2026Article
- Quercetin Alleviates Osteoarthritis Pain by Inhibiting Vascular Endothelial Growth Factor A Through Regulating cGAS/STING Pathway.Journal of cellular and molecular medicine · 2026Article
- Synovial immune control failure in osteoarthritis: from maintenance of tissue homeostasis to inflammatory niche formation.Frontiers in immunology · 2026Review
- Conservative Management of Focal Chondral Lesions of the Knee and Ankle: Current Concepts.Cells · 2025Review
- Dual-center study on AI-driven multi-label deep learning for X-ray screening of knee abnormalities.Scientific reports · 2025Article
- Piezo1 induces mitochondrial autophagy dysfunction leading to cartilage injury in knee osteoarthritis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Oxidative Stress, MicroRNAs, and Long Non-Coding RNAs in Osteoarthritis Pathogenesis: Cross-Talk and Molecular Mechanisms Involved.International journal of molecular sciences · 2025Review
- STAT3 Signaling Pathway in Health and Disease.MedComm · 2025Review
- Metabolic Profiles of Encapsulated Chondrocytes Exposed to Short-Term Simulated Microgravity.Annals of biomedical engineering · 2025Article
- From molecular mechanism to plant intervention: the bidirectional regulation of inflammation and oxidative stress in bone aging.Frontiers in endocrinology · 2025Review
- Synoviocyte-chondrocyte triculture model for early-stage PTOA: fibronectin fragment-induced catabolic effectsFrontiers in bioengineering and biotechnology · 2025Article
- Mode of injury and level of synovitis alter inflammatory chondrocyte gene expression and associated pathways.Scientific reports · 2024Article
- Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts.Cells · 2024Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundTraumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease.
methodsOsteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin's grade 0-2, 23-83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile.
resultsImmediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified.
conclusionCBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression.
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