Synovial pathology in an ovine model of osteoarthritis : effect of intraarticular hyaluronan (Hyalgan®)

Published scoring methods for quantifying synovitis focus on acute inflammatory parameters, and are unsuitable as outcome measures in experimental surgical models of osteoarthritis (OA). The aim of the present study was to define a modified histopathological scoring system for ovine synovium more suited to the chronic pathology induced by ovine meniscectomy, and to apply it to detect any therapeutic effects following intraarticular injection of hyaluronan (HA) (Hyalgan). OA was induced in 12 sheep by bilateral lateral meniscectomy, before weekly intraarticular injections of HA or saline vehicle from 16-20 weeks post-operatively, prior to sacrifice at 26 weeks. Six matched sheep were used as controls. Synovial sections were qualitatively scored for hyperplasia, inflammatory infiltrate, fibrosis, and hypervascularity; cell number, depth of fibrosis, and vessel number were also quantified using a graticule. OA synovia had significantly elevated scores for inflammatory cell infiltration, subintimal fibrosis, vascularity, and aggregate score relative to controls. HA-treated sheep had significantly lower vascularity score (p=0.015), aggregate score (p=0.007), depth of fibrosis (p=0.003) and vessel number (p=0.048) compared to saline-injected sheep. This study confirms the presence of a chronic synovitis in this OA model, characterised by subintimal fibrosis and hypervascularity (but only modest infiltrate and minimal intimal hyperplasia), which is partially ameliorated by intraarticular hyaluronate therapy.