Abstract
Objectives: The aims were to assess the contribution of arg-gly-asp (RGD) mediated cell integrin–matrix bonds to interstitial hydraulic resistance and to fenestrated endothelial permeability in joints. Joint fluid is generated by filtration from fenestrated capillaries and drains through a fibronectin-rich synovial intercellular matrix. The role of parenchymal cell–matrix bonding in determining tissue hydraulic resistance is unknown.
Methods: The knee cavity of anesthetized rabbits was infused with saline or the competitive hexapeptide blocker GRGDTP, with or without added osmotic stress (600 mosm saline). Intra-articular pressure Pj, net trans-synovial drainage rate s, and the permeation of Evans blue-labeled albumin (EVA) from plasma into the joint cavity were measured.
Results: GRGDTP increased the hydraulic conductance of the synovial drainage pathway, ds/dPj, by 71% (p =. 02, paired t test, n = 6 animals). Synovial plasma EVA clearance (control 7.1 ± 0.8 μL h−1, mean ± SEM, n = 15) was unaffected by GRGDTP (7.0 ± 2.3 μL h−1, n = 6) or hyperosmolarity (4.9 ± 1.5 μL h−1, n = 8) but was increased by GRGDTP and hyperosmolarity together (15.9 ± 4.8 μL h−1, n = 5) (p =. 01, ANOVA). Changes in dPj/dt evoked by GRGDTP plus hyperosmolarity, but neither alone, demonstrated increased microvascular filtration into the joint cavity (p <. 001, ANOVA), as did changes in fluid absorption from the infusion system at fixed Pj.
Conclusions: RGD-mediated bonds between the parenchymal cells and interstitial polymers reduce the interstitial hydraulic conductance by 42%. This helps to retain the lubricating fluid inside a joint cavity. RGD-mediated bonds also support the macromolecular barrier function of fenestrated endothelium, but in vivo this is evident only in stressed endothelium (cf. in vitro).