Smith MM et al. - Increased fibrosis and vascularity are hallmarks of pathological change in synovium. Both the intra-articular hyaluronan (IA HA) and an amide derivative of HA reduced aspects of this pathology thus providing a potential mechanism for improving joint mobility and function in OA. Methods
Study to assess the pathological changes in the synovium of an ovine model of OA and to evaluate the effects of two HA preparations on this pathology
18 sheep had bilateral lateral meniscectomy to induce OA
4 mos post-surgery animals received IA saline or HA/wk x5wks or 3 injections of an amide derivative of HA every 2 wks
6 mos after meniscectomy, sheep were killed, knee joint synovium processed
Sections of synovium from normal and treated joints were also immunostained for TNF-α, HSP-47, TGF-β, CD44, CTGF or iNOS
HA synthesis by synovial fibroblasts isolated from each OA joint was quantified
Results
Aggregate scores of pathological change were higher in OA joint synovia vs controls, with individual measures of subintimal fibrosis and vascularity predominantly affected
Depth of intimal fibrosis was also higher in meniscectomized joints
IA treatment with HA decreased aggregate score, vascularity and depth of fibrosis
HYADD®4-G treatment decreased vascularity, intimal hyperplasia and increased high-molecular weight HA synthesis by synovial fibroblasts
CD44, CTGF or iNOS expression was increased in the synovial lining of OA joints vs normal, but no modulation of this increase by either HA preparation
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