Structural Associations of Symptomatic Knee Osteoarthritis

Abstract

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

PKCδnull mutations in a mouse model of osteoarthritis alter osteoarthritic pain independently of joint pathology by augmenting NGF/TrkA-induced axonal outgrowth

“…Our findings complement previous studies that indicate that NGF and chemokines are produced by inflamed fibroblast-like synovial cells and human OA chondrocytes. [28][29][30] In addition, an increase in levels of NGF in human OA may promote angiogenesis and osteochondral vascularity. 31 Based on these collective findings, it appears that increased amounts of NGF detected in arthritic synovial fluid 32 could result from the cumulative levels of NGF secreted from several distinct joint tissues.…”

The time has come to incorporate a greater focus on rate of force development training in the sports injury rehabilitation process

“…Synovitis is considered as one of the important local biological factors for symptomatic OA 4,29 . In our study with two different histological observations, we could note the significant reduction in the synovitis in intervention knees compared to control knees.…”

Emerging targets in osteoarthritis therapy

“…The invasive vascular elements in calcified cartilage and synovium may serve as conduits for nerve fibers and stimuli for nerve growth factor (NGF) [122]. VEGF is expressed by chondrocytes in proximity to the angiogenesis, suggesting that it is involved in recruiting vascular elements.…”