All ETDs from UAB

Advisory Committee Chair

Elie Ghanem

Advisory Committee Members

Jake Chen

Chander Raman

Rosa Serra

Andrzej Slominski

Document Type

Dissertation

Date of Award

2023

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

The overall risk of infection after total knee arthroplasty (TKA) has not improved over the past 20 years, remaining 10-40 times greater than the risk of infection of a native knee. Despite extensive research into periprosthetic joint infection (PJI), little is known about the synovial fluid immune homeostasis of the native knee joint and how TKA surgery itself impacts the local immune composition. While many postulate a role for cartilage in maintaining this immune homeostasis, the exact method in which it contributes remains elusive. Therefore, in this dissertation I have investigated the synovial fluid changes occurring in the knee joint associated with TKA surgery compared to native knees, in the first comprehensive study to compare each of the 5 study groups directly in human patients. We discovered numerous differences within the synovial fluid of the knee joint during the various stages associated with TKA surgery. Importantly, alterations to the synovial concentration of multiple vitamin D compounds including decreased 1,25(OH)2 D3, 20(OH)D3, 1,20,23(OH)3D3 occurs with TKA surgery that are associated with decreased monocytes and non-significant decreases in DEFB4, an antimicrobial peptide involved in pathogen eliminate as an innate defense mechanism. The reason for these vitamin D changes may be related to the removal of cartilage during TKA, as we demonstrate that chondrocytes constitutively express genes for vitamin D metabolism-related enzymes including CYP27A1, CYP2R1, and CYP27B1 of the canonical pathway and CYP11A1 of the non-canonical pathway. We confirmed that primary chondrocytes produce all investigated vitamin D compounds when exposed to vitamin D3, further supporting the theory cartilage is contributing to the local immune homeostasis through vitamin D metabolism. Despite many additional novel findings, the totality of our work provides novel information on synovial vitamin D metabolism and the overall role cartilage plays within the joint, suggesting vitamin D alterations may play a crucial role in maintaining the local synovial homeostasis worthy of further study. This exploratory work lays the foundation for future investigation into the mechanistic pathways driving the identified changes in the synovial fluid of the knee after TKA surgery.

Available for download on Thursday, May 09, 2024

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