Synovial tissue inflammation in early and late osteoarthritis

Maria J Benito ¹, Douglas J Veale ¹, Oliver FitzGerald ¹, Wim B van den Berg ² and Barry Bresnihan ^1*

¹ St Vincent's University Hospital, Elm Park, Dublin, Ireland
² University Medical Centre, Nijmegen, The Netherlands

^* To whom correspondence should be addressed. E-mail: b.bresnihan{at}svcpc.ie.

Accepted 7 February 2005

Abstract

Objective: The aim of this study was to compare selected immunohistologic features of inflammation in synovial tissue obtained from patients with early and late osteoarthritis (OA).

Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were employed to quantify the microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation and angiogenic factors, nuclear factor-B (NF-B) activation, expression of tumour necrosis factor- (TNF and interleukin-1 (IL-1) and the presence of cyclooxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in-vitro production of prostaglandin E2 (PGE2)

Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p=0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p=0.01), vascular endothelial growth factor (VEGF) (p=0.001) and intercellular adhesion molecule-1 (ICAM-1) expression (p<0.001). The numbers of TNF and IL- 1-producing cells were also significantly greater in early OA (p<0.001). The manifestations of inflammation in early OA were associated with increased expression of both the NF-B1 (p<0.001) and RelA (p=0.015) subunits, and with increased COX-2 expression (p=0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups.

Conclusion: Increased mononuclear cell infiltration and over-expression of mediators of inflammation were observed in early OA, compared to late OA. Isolated FLS were functionally similar in both groups, consistent with micro-environmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.

Keywords: early osteoarthritis, inflammation, osteoarthritis, synovitis

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