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Rheumatology Advance Access published online on June 19, 2008
Rheumatology, doi:10.1093/rheumatology/ken219
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Significant synovial pathology in a meniscectomy model of osteoarthritis: modification by intra-articular hyaluronan therapy

M. M. Smith1, M. A. Cake2, P. Ghosh1, A. Schiavinato3, R. A. Read2 and C. B. Little1

1Raymond 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, 2School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA, Australia and 3Fidia S.p.A., Abano Terme, Italy.

Correspondence to: M. M. Smith, Raymond Purves Bone and Joint Research Laboratories, Level 5, University Clinic, Royal North Shore Hospital, St Leonards NSW 2065, Australia. E-mail: mobsmith{at}med.usyd.edu.au


  Abstract

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-β, 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.

Conclusion. 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.

KEY WORDS: Osteoarthritis, Animal model, Synovium, Hyaluronan

Submitted 13 November 2007; revised version accepted 12 May 2008.
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