Affiliation:
1. University of Pennsylvania Perelman School of Medicine, Orthopaedic Surgery Philadelphia Pennsylvania USA
2. Department of Veterans Affairs CMCVAMC Philadelphia Pennsylvania USA
3. Department of Bioengineering University of Pennsylvania Philadelphia Pennsylvania USA
4. Department of Orthopaedics Emory University Decatur Georgia USA
Abstract
AbstractMeniscus tears represent a common orthopedic injury that often requires surgery to restore pain‐free function. The need for surgical intervention is due, in part, to the inflammatory and catabolic environment that inhibits meniscus healing after injury. In other organ systems, healing is dependent on the migration of cells to the site of injury; however, in the meniscus, it is currently unknown how the microenvironment dictates cell migration in the postinjury inflamed setting. Here, we investigated how inflammatory cytokines alter meniscal fibrochondrocyte (MFC) migration and sensation of microenvironmental stiffness. We further tested whether an FDA approved interleukin‐1 receptor antagonist (IL‐1Ra; Anakinra) could rescue migratory deficits caused by inflammatory challenge. When cultured in the presence of inflammatory cytokines (tumor necrosis factor‐α [TNF‐α] or interleukin‐1β [IL‐1β]) for 1 day, MFC migration was inhibited for 3 days before returning to control levels at Day 7. This migratory deficit was clear in three‐dimensional as well, where fewer MFCs exposed to inflammatory cytokines migrated from a living meniscal explant compared with control. Notably, addition of IL‐1Ra to MFCs previously exposed to IL‐1β restored migration to baseline levels. This study demonstrates that joint inflammation can have negative impacts on meniscus cell migration and mechanosensation, affecting their potential for repair, and that resolution of this inflammation with concurrent anti‐inflammatories can reverse these deficits. Future work will apply these findings to mitigate the negative consequences of joint inflammation and promote repair in a clinically relevant meniscus injury model.
Funder
U.S. Department of Veterans Affairs
National Institutes of Health
Subject
Orthopedics and Sports Medicine
Cited by
1 articles.
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1. Molecular Biology of Meniscal Healing: A Narrative Review;International Journal of Molecular Sciences;2024-01-07