Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Supervisor

Degen, Ryan M.

2nd Supervisor

Brackstone, Muriel

Co-Supervisor

Abstract

Objective: The objective of this thesis was to provide insight into early changes in osteoarthritis pathogenesis. Histopathology of synovium was investigated in femoroacetabular impingement (FAI), FAI with early hip osteoarthritis, and advanced hip osteoarthritis.

Methods: Synovium biopsies were collected from ten FAI, fourteen FAI with early osteoarthritis, and twelve advanced osteoarthritis patients. Histopathological grading allowed assessment of osteoarthritis-associated features. Microvessel density and maturity were determined through immunofluorescent labelling of CD31 and a-smooth muscle actin. Immunohistochemical staining was applied to calculate CD105+ microvessel density.

Results: In all groups, vascularization was prominent, with a mean [95% confidence interval] of 1.66 [1.41, 1.91]. Mature density was greater than immature (83.84 [64.14, 103.55] versus 13.12 [9.46, 16.78] microvessels/mm2). Low CD105+ density (3.06 [0.78, 5.34] microvessels/mm2) suggests microvessel inactivity.

Conclusion: Mature, inactive microvasculature was prominent across this spectrum of hip osteoarthritis. These findings support the theory of differences between hip and knee osteoarthritis pathophysiology.

Summary for Lay Audience

Femoroacetabular impingement (FAI) is a hip disorder characterized by deformities of the femoral head (“ball”) and acetabulum (“socket”) and is observed mainly in young people. Furthermore, FAI is a risk factor for developing hip osteoarthritis (OA). Because FAI is seen in young patients, studying this condition as it relates to OA may provide the ability to determine disease processes occurring early in hip OA development.

Osteoarthritis is a joint disease accompanied by loss of cartilage and degeneration of bone. Recent research has determined that interactions between cartilage, bone, and synovium are crucial for maintaining joint health. When changes in these structures arise, OA can follow. Synovium is a thin membrane in close contact with the joint space and is responsible for producing synovial fluid to nourish cartilage and remove waste from the joint environment. Abnormal changes occur in osteoarthritic synovium, but few studies have considered these in FAI patients. Therefore, we studied microscopic features in synovium from patients with FAI, FAI and early hip OA, and severe hip OA to determine whether OA-associated synovial changes occur in FAI.

We analyzed seven features that are observed in OA synovium. The most prominent feature we observed was vascularization (increased blood vessels), which was similarly present in all groups. To investigate blood vessels further, we looked for evidence of whether they were fully matured vessels, or immature vessels. In all groups, mature vessels predominated. We also determined that these vessels are largely inactive.

This thesis includes the first study to report on several features in FAI synovium, including features describing abnormal small vessels. We observed these features to varying extents in all groups. Based on our findings, hip synovium in FAI patients contains small blood vessels that are mostly mature and inactive. This differs from previous findings reported in knee OA synovium, where many small vessels were immature and active. Future studies should investigate whether any cases of FAI are marked by immature and active small vessels, or whether our findings are generalizable. Furthermore, studies should investigate potential causes for differences between our observed hip synovium vessels, and those of knees.

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