The effect of infectious and inflammatory stimuli on the synovium and resident synovial macrophages in a novel human explant model 9007
Year: 2025
Type: article
Abstract: Description The annual healthcare cost of arthritis in the US is approximately $300 billion, and we are unable to prevent or reverse cartilage damage. This damage is likely caused by inflammation secondary to immune cell activity in the joint space. Our objective is to understand the underlying mechanisms of infectious and inflammatory arthritis. To study the inflammatory origin of human arthritis, we created an ex vivo model that recapitulates changes to the synovium seen in vivo. This system allows us to explore the changes to the unique immune cells lining the joint space: resident synovial macrophages (RSMs). RSMs are bound together by tight junctions into an intimal lining that protects the joint space from inflammation. Here, we demonstrate that infectious (Lipopolysaccharide, LPS) and inflammatory (Monocyte Chemoattractant Protein-1, MCP-1) stimuli disrupt synovial architecture. Specifically, LPS thinned the intimal lining while MCP-1 thickened it, and this may correspond with loss or gain of cells respectively. Both treatments decreased intimal border integrity. We conclude that observed changes in the synovial architecture are indicative of disruption to the protective joint lining. This would potentially allow circulating cells to gain entry to synovial fluid, thereby causing inflammatory damage to cartilage, bone, and synovium. Topic Categories Immune Mechanisms of Human Disease (HUM)
Source: The Journal of Immunology
Authors: Katherine Lea Butler, Christy Petersen, Jacob Elkins, Rachel Johnson, Karen I. Cyndari
Institutions: University of Iowa, The Ohio State University
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416447561
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