Influence of Actin Cytoskeleton on Intra-articular and Interstitial Fluid Pressures in Synovial Joints

Abstract

Fibroblast microfilamentous actin (F-actin) influences interstitial fluid pressure via linkages to collagen in rat skin (Berg et al., 2001). The present aims were to determine whether the actin cytoskeleton of synovial endothelium, fibroblasts, and synoviocytes influences in vivo (i) fluid exchange between a joint cavity and synovial microcirculation and (ii) extracellular fluid pressures in joints. Rabbit knee joints were treated intra-articularly with the Factin disrupting drugs cytochalasin D and latrunculin B while joint fluid pressure P j was recorded. In joints injected with small volumes of control solution, P j fell with time (؊0.05 ؎ 0.01 cm H 2 O min ؊1 , mean ؎ SEM, n ‫؍‬ 9, equivalent drainage rate 3.9 l min ؊1 ). Cytochalasin or latrunculin reversed this in ϳ4 min in vivo; P j increased with time, e.g., ؉0.12 ؎ 0.04 cm H 2 O min ؊1 at 200 M cytochalasin (equivalent filtration rate into joint 6.6 -12.5 l min ؊1 , n ‫؍‬ 4), with a cytochalasin EC 50 of 45 M. Plasma ␥-globulin clearance into the joint cavity was also increased. Post mortem, cytochalasin did not reverse dP j /dt and had no more effect on P j than did control solution. Also, when synovial interstitial fluid pressures were measured by servonull micropipette post mortem (control ؊0.95 ؎ 0.37 cmH 2 O, n ‫؍‬ 18) cytochalasin had no significant effect on interstitial pressure over 60 min, even at 1 mM. It was concluded that synovial endothelial F-actin has an important role in the normal synovial microvascular resistance to fluid filtration and plasma ␥-globulin permeation and is thus a potential link between pro-in-

Contribution of F‐Actin to Barrier Properties of the Blood‐Joint Pathway

“…The study extends a recent investigation of changes in intra-articular pressure and matrix interstitial pressure following F-actin disruption (40). The latter investigation indicated that actin disassembly raised capillary filtration rate and ␥-globulin permeation, but that synoviocyte F-actin disassembly had no detectable effect on interstitial fluid pressure post mortem, in contrast to the findings of Berg et al (5) in rat skin.…”

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

“…It may, however, not be a general mechanism for edema formation, since there was no effect on P if in the rabbit synovium after disrupting the cytoskeleton by cytochalasin D treatment, although resulting in hyperfiltration into the joint mimicking an inflammatory reaction (368).…”

Ballistic intracellular nanorheology reveals ROCK-hard cytoplasmic stiffening response to fluid flow

“…Endothelial cells adapt to shear flow by forming extended Factin stress fibers that align in the direction of flow (Girard and Nerem, 1995;Langille et al, 1991;Malek and Izumo, 1996) and polarize by reorganizing the microtubule network to reposition the centrosome in the direction of flow (Tzima et al, 2003;Wojciak-Stothard and Ridley, 2003). Shear flows also cause changes in actin and microtubule structures in myofibroblasts and fibroblasts (Lee et al, 2005;Ng et al, 2005;Ng and Swartz, 2003;Poli et al, 2001), and influence their nuclear-receptor distributions and nucleus movement (Ji et al, 2003;Tseng et al, 2004). Reorganizations of cytoskeletal structures in endothelial cells and fibroblasts are coupled to the activity of members of the Rho GTPase family, including RhoA, Rac1 and Cdc42 (Hall, 1998;Nobes and Hall, 1995;.…”