Leukocyte adhesion molecules modulate inflammation of cartilage in joint trauma

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DESCRIPTION (provided by applicant): Blunt trauma to a joint is commonly associated with swelling, hemarthrosis and pain as result of injury to the surrounding tissues. Influx of leukocytes into the joint can cause a secondary insult to already traumatized articular cartilage which may predispose the joint to develop post-traumatic arthritis. My preliminary studies found that when autologous leukocytes were co-cultured with traumatized cartilage they caused more matrix damage and cell death. My main hypothesis is that mechanical trauma to the articular cartilage will expose matrix attachment sites for leukocytes to adhere to the matrix, and also expose chondrocyte ligands, both of which will result in the leukocytes and chondrocytes excreting inflammatory cytokines to further degrade the cartilage. I will use a bovine explant model to characterize how the severity of the mechanical trauma to the cartilage modulates the degree of the inflammatory response. I will also identify specific adhesion molecules on leukocytes (neutrophils, monocytes and lymphocytes) that facilitate interaction with traumatized articular cartilage to cause the inflammatory response in the tissue. To test these hypotheses I will apply different levels of trauma to cartilage and incubate cartilage with autologous peripheral blood leukocyte subpopulations with and without the presence of blocking antibodies for adhesion molecules (CD18, CD29 and Lselectin). These experiments will be performed at the cellular level by monitoring cell viability, inflammatory cytokines (IL-1, TNF-a, NO, PGE2) and matrix enzymes (MMP, aggrecanase, matrix loss), and at the structural level by analyzing the extracellular matrix (biomechanical properties properties, histology). The etiology of post-traumatic osteoarthritis is not completely known. It is a joint disease that affects all ages, particularly young and middle-aged adults. Joint trauma and articular cartilage survival remains a very serious clinical problem. Proposed study will give us a better understanding of the association between inflammatory events and the biological processes occurring in the joint after blunt trauma. PUBLIC HEALTH RELEVANCE: Project Narrative Joint arthritis can occur as a result of a joint injury. Why the articular cartilage with our joints wakens down as a result of the trauma is not well understood. Post-traumatic arthritis is a syndrome of joint degeneration and dysfunction that affects all ages, particularly young and middle-aged adults. Of the foremost importance is to first understand the mechanisms how acute inflammation can predispose joint to develop post-traumatic arthritis which will be essential for the improving the quality of life for patients by developing treatment modalities.