Significant synovial pathology in a meniscectomy model of osteoarthritis: modification by intra-articular hyaluronan therapy.
OBJECTIVE
IA therapy with hyaluronan (HA) is reported to provide symptomatic relief and disease modification in OA. This study assessed the pathological changes in the synovium of an ovine model of OA and evaluated the effects of two HA preparations on this pathology.


METHODS
Eighteen sheep had bilateral lateral meniscectomy to induce OA. Four months post-surgery animals received IA saline or HA (Hyalgan) weekly for 5 weeks or three injections of an amide derivative of HA (HYADD 4-G) every 2 weeks (n = 6 per group). Six months after meniscectomy, sheep were killed, knee joint synovium processed, scored for pathological change and compared with synovium from non-operated animals. Sections of synovium from normal and treated joints were also immunostained for TNF-alpha, HSP-47, TGF-beta, CD44, connective tissue growth factor (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 compared with controls, with individual measures of subintimal fibrosis and vascularity predominantly affected. Depth of intimal fibrosis was also significantly higher in meniscectomized joints. IA treatment with Hyalgan 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 compared with normal, but there was no significant modulation of this increase by either HA preparation.


CONCLUSIONS
Increased fibrosis and vascularity are hallmarks of pathological change in synovium in this meniscectomy model of OA. Both the 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.
Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia. mobsmith@med.usyd.edu.au
M M
MM
Smith
M A
MA
Cake
P
P
Ghosh
A
A
Schiavinato
R A
RA
Read
C B
CB
Little
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000096:biosynthesis / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008592:Menisci, Tibial / Q000601:surgery; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D034561:Sheep, Domestic; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*
D006820:Hyaluronic Acid