EFFECT OF DEPLETION OF GLYCOSAMINOGLYCANS AND NONCOLLAGENOUS PROTEINSON INTERSTITIAL HYDRAULIC PERMEABILITY IN RABBIT SYNOVIUM

1. The hydraulic resistance of synovial interstitium helps to retain a lubricating fluid within the joint cavity. The contributions of sulph ated glycosaminoglycans to resistance were assessed by selective deple tion by chondroitinase ABC, keratanase and heparinases I, II and III i n vivo. Also, since glycosaminoglycans do not account fully for the re sistance, the contribution of non-collagenous, structural proteins in interstitium was assessed by treatment with chymopapain, a collagen-sp aring protease. 2. Ringer solution containing enzyme was injected into the synovial cavity of the knee in anaesthetized rabbits. After great er than or equal to 30 min the intra-articular pressure was raised and the relation between pressure (P-j) and trans-synovial outflow (Qover dot(s)) determined. The slope dQover dot(s)/dP(j) at low pressures, i .e. below yield pressure, represents the hydraulic conductance of the lining, i.e. 1/resistance. The contralateral joint received Ringer sol ution without enzyme as a control. Action of enzymes on the tissue was confirmed by histochemical and immunohistochemical studies. 3. Treatm ent with chondroitinase ABC (5 joints) increased the hydraulic conduct ance of the lining by 2.3 times (control, 1.34 +/- 0.22 mu l min(-1) c mH(2)O(-1); post-enzyme, 3.11 +/- 0.45 mu l min(-1) cmH(2)O(-1)). This was significantly less than the effects of leech, Streptomyces and te sticular hyaluronidases, which caused an average 4.7 times increase (P < 0.001, ANOVA). Analogous findings were made above yield pressure. 4 . Treatment with keratanase (3 joints) or heparinases I, II and III (3 joints) caused no significant increase in trans-synovial flows or con ductance, even though the concentration of heparan sulphate in synoviu m is higher than that of chondroitin sulphates or hyaluronan. 5. Treat ment with chymopapain (7 joints) caused the greatest increases in tran s-synovial flow, which exceeded control flow by an order of magnitude in one case. After 0.1 U chymopapain the average conductance was 6.6 t imes the control conductance below yield pressure. Immunohistochemical studies confirmed that chymopapain treatment removed the synovial pro teoglycans. 6. It is concluded that, despite their similar resistiviti es in vitro, the different glycosaminoglycans do not contribute equall y, weight for weight, to interstitial resistance in vivo. Hyaluronan i s the dominant glycosaminoglycan governing synovial interstitial resis tance. In addition, non-collagenous structural proteins contribute sig nificantly to interstitial resistance.