The basic and research progress of joint barrier dysfunction in joint diseases
Year: 2025
Type: article
Abstract: Biological barriers are pivotal in safeguarding organisms against external threats while preserving internal homeostasis. Among these, the joint barrier—comprising synovium, vascular systems, articular cartilage, and subchondral bone—plays a critical yet underexplored role in joint health and disease. Emerging evidence implicates joint barrier dysfunction in the pathogenesis of osteoarthritis (OA), rheumatoid arthritis (RA), hemophilic arthropathy, and gouty arthritis (GA), driven by immune dysregulation, vascular permeability alterations, and metabolic reprogramming. This review systematically delineates the anatomical and molecular underpinnings of joint barrier disorders to unravel synovial cellular heterogeneity and intercellular crosstalk. We highlight how synovial fibroblast (FLS), macrophage, and endothelial cell orchestrate immune infiltration, exacerbating synovitis and cartilage degradation. Epigenetic modifications and immunometabolic shifts further disrupt barrier integrity, perpetuating chronic inflammation. Crucially, this work advances a translational roadmap by proposing targeted strategies: (1) gene therapy modulating inflammatory pathways and cytokine inhibitors; (2) nanotechnology-driven drug delivery systems for precise anti-inflammatory targeting; and (3) regenerative approaches leveraging biomaterials and stem cells to restore cartilage integrity. Future directions emphasize resolving unresolved complexities, including spatiotemporal macrophage polarization dynamics, FLS epigenetic reprogramming, and systemic cross-talk (gut-joint axis, neuroimmune interactions). By bridging mechanistic insights with therapeutic innovation, this review underscores the joint barrier as a linchpin for developing next-generation interventions in inflammatory and degenerative joint diseases.
Institution: First Affiliated Hospital of Jinan University
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4413805015