Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Acute Meniscal Injury Is Associated with Synovial Inflammation: Cellular and Molecular Characterization of Synovitis
Scanzello1, Carla R., McKeon2, Brian P., Umoh3, Eva, Swaim2, Bryan, DiCarlo3, Edward F., Hunter2, David J., Richmond2, John C.
Synovitis is related to pain in patients with osteoarthritis (OA), but little is known regarding synovial responses in patients with acute meniscal injury, which predisposes to development of OA. A prospective study was designed to examine histological and molecular changes in synovium (SM) in patients with acute meniscal injury presenting for menisectomy.
24 patients (16 M/8F, median age 47, range 2160) with acute meniscal tears without clinical or radiographic evidence of pre-existent OA underwent arthroscopy. SM biopsies were obtained from the medial and lateral gutters and suprapatellar pouch. Biopsies were processed for histology and RNA analysis. On H&E staining, six histopathologic features were scored: perivascular inflammation, vascularity, detritis, fibrosis, perivascular edema and SM hyperplasia. Scores were compared to patients with pre-existing OA (n=18) from an additional study sample. RNA was prepared for microarray analysis from a subset of patients. Affymetrix U133 + 2.0 chips were used, data analyzed using Genespring software, and pathway over-representation analysis carried out with a focus on innate immune responses.
23 biopsies at each location (n = 69) were analyzed. Of the histologic features evaluated, synovial hyperplasia (40/69, 58%) was most common, and perivascular inflammation was observed in 32% of biopsies. The spectrum of histologic change was similar to OA, though inflammatory scores were lower in the acute meniscal injury group. From histology, we identified patients with or without inflammation and performed microarray analysis on 8 representative samples. Comparative analysis of gene expression in inflammatory vs. noninflammatory samples demonstrated 260 genes differentially expressed >= 2.0 fold, p<0.05. Molecular signatures consistent with lymphocyte activation and recruitment were observed. Of note, chemokines involved in cellular trafficking and common-gamma chain cytokine signaling components were enriched in the inflammatory biopsies.
Comparison of expression patterns in patients with or without histologic inflammation revealed enrichment of chemokine and cytokine signaling pathways associated with lymphocyte recruitment and activation in the inflammatory SM biopsies. These patients are being followed longitudinally to determine whether SM inflammation patterns are predictive of post-operative clinical course. Characterization of the cellular and molecular processes associated with joint injury could lead to novel therapeutic approaches for reducing the risk of post-traumatic OA.
To cite this abstract, please use the following information:
Scanzello, Carla R., McKeon, Brian P., Umoh, Eva, Swaim, Bryan, DiCarlo, Edward F., Hunter, David J., et al; Acute Meniscal Injury Is Associated with Synovial Inflammation: Cellular and Molecular Characterization of Synovitis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :832