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This Article Full Text Full Text (PDF) All Versions of this Article: 578/1/291    most recent jphysiol.2006.119446v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sabaratnam, S. Articles by Levick, J. R. Search for Related Content PubMed PubMed Citation Articles by Sabaratnam, S. Articles by Levick, J. R. Related Collections Cardiovascular

¹ Physiology, Basic Medical Sciences, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
² Division of Medicine, Imperial College, Hammersmith Hospital, London W12 0NN, UK

Hyaluronan (HA) retention inside the synovial cavity of joints serves diverse protective roles. We tested the hypothesis that HA retention is mediated by the network of extracellular matrix proteins in the synovial lining. Cannulated rabbit knee joints were infused with HA solution with or without pretreatment by chymopapain, a collagen-sparing protease. Trans-synovial fluid escape rate was measured and, after a period of trans-synovial filtration, samples of intra-articular fluid and subsynovial fluid were analysed for HA to assess its trans-synovial ultrafiltration. In control joints, HA ultrafiltration was confirmed by postfiltration increases in intra-articular HA concentration (259 ± 17% of infused concentration) and reduced subsynovial concentration (30 ± 8%; n = 11). The proportion of HA molecules reflected by the synovium was 57–75%. Chymopapain treatment increased the hydraulic permeability of the synovial lining 13-fold, almost abolished the trans-synovial difference in HA concentration and reduced the HA reflected fraction to 3–7% (n = 6; P < 0.001, ANOVA). Structural studies confirmed that chymopapain treatment depleted the matrix of proteoglycans but preserved its collagen. The findings thus demonstrate that HA ultrafiltration and synovial hydraulic permeability are determined by the network of non-collagen, extracellular matrix proteins. This may be important clinically, since protease activity is raised in rheumatoid arthritis, as are HA and fluid escape.

(Received 17 August 2006; accepted after revision 27 September 2006; first published online 28 September 2006)
Corresponding author J. R. Levick: Physiology, Basic Medical Sciences, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. Email: jlevick{at}sghms.ac.uk