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Structural Associations of Symptomatic Knee Osteoarthritis: Structural Associations of Symptomatic Knee OA

Stoppiello, Laura A.; Mapp, Paul I.; Wilson, Deborah; Hill, Roger; Scammell, Brigitte E.; Walsh, David A.


Laura A. Stoppiello

Paul I. Mapp

Deborah Wilson

Roger Hill

Brigitte E. Scammell

Professor of Rheumatology



Structural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA.


Medial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group). To identify features of OA, we compared the patients with advanced OA with the age-matched non-OA controls (n = 26 per group). To identify OA features associated with symptoms, we compared two additional groups of subjects who were matched for severity of chondropathy (n = 29 per group): patients undergoing TKR for symptomatic OA (symptomatic chondropathy group) and postmortem subjects with similar severity of chondropathy who were asymptomatic during the last year of life (asymptomatic chondropathy group). The histologic features of the samples were graded, and immunoreactivities for macrophages (CD68) and nerve growth factor (NGF) in the synovium were quantified. The cellular localization of synovial NGF was determined by double immunofluorescence analysis.


Advanced OA cases displayed more severe changes in the synovium (synovitis, increased synovial NGF, and CD68-immunoreactive macrophages) and cartilage (loss of cartilage surface integrity, loss of proteoglycan, tidemark breaching, and alterations in chondrocyte morphology) than did the non-OA controls. Synovial NGF was localized predominantly to fibroblasts and to some macrophages. The symptomatic chondropathy group displayed greater levels of synovitis, synovial NGF, and loss of cartilage integrity, in addition to alterations in chondrocyte morphology, than did the asymptomatic chondropathy group (P < 0.05 for each comparison).


Synovitis, increased synovial NGF, alterations in chondrocyte morphology, and loss of cartilage integrity are features of knee OA that may be associated with symptoms.


Stoppiello, L. A., Mapp, P. I., Wilson, D., Hill, R., Scammell, B. E., & Walsh, D. A. (2014). Structural Associations of Symptomatic Knee Osteoarthritis: Structural Associations of Symptomatic Knee OA. Arthritis and Rheumatology, 66(11), 3018-3027.

Journal Article Type Article
Acceptance Date Jul 3, 2014
Online Publication Date Oct 26, 2014
Publication Date 2014-11
Deposit Date Oct 31, 2016
Publicly Available Date Oct 31, 2016
Journal Arthritis & Rheumatology
Print ISSN 2326-5191
Electronic ISSN 2326-5205
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 66
Issue 11
Pages 3018-3027
Public URL
Publisher URL


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