Abstract
Hydraulic resistance of interstitium is of major importance in body fluid distribution. In the synovial lining it is vital for the retention of intra-articular fluid, and is attributed chiefly to the network of interstitial biopolymers occupying intercellular gaps in the tissue. Selective removal of synovial hyaluronan (HA) by protease-free hyaluronate lyase results in an almost 10× increase in synovial hydraulic permeability from 0.48 ± 0.24 μ L min−1cm H2O (control) to 4.56 ± 0.40 μ L min−1 cm H2O (mean ± SD, n = 6 rabbits, p < .001, t test) leading to the hypothesis that hyaluronan plays a major role in the organization of interstitial matrix structure. To test whether removal of hyaluronan causes significant changes in synovial ultrastructure, morphometry of hyaluronidase-treated synovium was carried out. Following hyaluronidase, the thickness of the synovial lining was reduced from 13.0 ± 1.6 μ m (control) to 10.6 ± 1.6 μ m (mean ± SD throughout, n = 50 measurements per rabbit, 6 rabbits. p < .001, t test). This was accompanied by a significant reduction of synovial interstitial volume fraction from 76.2 ± 20.6% (control) to 67.04 ± 24.94% (p < .001, t test), and an increase in collagen bundle volume as a fraction of interstitial volume from 40.75 ± 4.97% (control) tissue to 48.77 ± 11.72% (p < .0001, t test). The findings indicate that the removal of hyaluronan chains leads to morphological disruption. Thus, hyaluronan chains play a major role in the organization of synovial structure. The observed morphological changes are insufficiently large to explain fully the great rise in hydraulic permeability observed on HA removal. The latter is likely to be due to disruption of tertiary architecture at the molecular organization level.
The author thanks R. Moss of the Image Resource Facility at St George's for his expertise and advice in electron microscopy, morphometric, and photographic techniques. I also thank J. R. Levick for his helpful advice and comments, and for reading the manuscript. This work was funded by the Wellcome Trust (056983/Z/99).