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Wyatt, Laura A. (2015) Structural associations of symptomatic knee osteoarthritis. PhD thesis, University of Nottingham.

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Abstract

Background: Pain is the major symptom of osteoarthritis (OA), however, the link between OA knee pain and pathology is incompletely understood. Furthermore, the earliest pathological changes in OA are difficult to characterise. The major aim of this thesis was to better understand the role of knee joint pathology in OA pain.

Methods: Medial tibial plateaux and synovium samples were obtained at total knee replacement (TKR) surgery for OA, or post-mortem (PM). To identify features associated with symptoms, tissue was compared from 29 TKR patients and from 29 PM cases with similar severity of chondropathy who did not report symptoms. Immunohistochemical and microarray techniques determined molecular changes in synovium that are associated with symptoms.

To determine early features of OA, histological scores for cartilage, subchondral and synovial inflammation (synovitis) were compared between non-arthritic controls, early OA and TKR cases. Latent class analysis classified subgroups of PM and TKR cases based on histopathological criteria.

Results: Symptomatic OA was associated with synovitis and increase in synovial nerve growth factor (NGF) (P< 0.05 for each comparison). Microarray analysis of the synovium revealed an up-regulation of various inflammatory which may explain an association between synovitis and pain.

Tidemark breaching was more common in early knee OA compared to non-arthritic controls, whereas synovitis and subchondral bone marrow replacement were more common in end-stage compared to early OA cases. Latent class analysis identified a subgroup of people with mild chondropathy and absence of synovitis, and 2 subgroups with established chondropathy distinguished by synovitis severity.

Discussion:. Symptomatic OA was associated with histological synovitis. Within the synovium, up-regulation of pro-nociceptive molecules might mediate the association between synovitis and pain. Furthermore, the severity of synovitis defines subgroups of patients with established chondropathy. Better understanding of the structural features that are associated with symptomatic OA may help develop structure-modifying treatments.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Walsh, D.A. Scammell, B.E.
Keywords:	Osteoarthritis, Knee, Pain, Synovitis, NGF
Subjects:	W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	30681
Depositing User:	Wyatt, Dr Laura
Date Deposited:	04 Feb 2016 11:57
Last Modified:	06 May 2020 14:48
URI:	https://eprints.nottingham.ac.uk/id/eprint/30681

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