A model of synovial fluid lubricant composition in normal and injured joints

Abstract

The synovial fluid (SF) of joints normally functions as a biological lubricant, providing low-friction and low-wear properties to articulating cartilage surfaces through the putative contributions of proteoglycan 4 (PRG4), hyaluronic acid (HA), and surface active phospholipids (SAPL). These lubricants are secreted by chondrocytes in articular cartilage and synoviocytes in synovium, and concentrated in the synovial space by the semi-permeable synovial lining. A deficiency in this lubricating system may contribute to the erosion of articulating cartilage surfaces in conditions of arthritis. A quantitative intercompartmental model was developed to predict in vivo SF lubricant concentration in the human knee joint. The model consists of a SF compartment that (a) is lined by cells of appropriate types, (b) is bound by a semi-permeable membrane, and (c) contains factors that regulate lubricant secretion. Lubricant concentration was predicted with different chemical regulators of chondrocyte and synoviocyte secretion, and also with therapeutic interventions of joint lavage and HA injection. The model predicted steady-state lubricant concentrations that were within physiologically observed ranges, and which were markedly altered with chemical regulation. The model also predicted that when starting from a zero lubricant concentration after joint lavage, PRG4 reaches steady-state concentration ~10-40 times faster than HA. Additionally, analysis of the clearance rate of HA after therapeutic injection into SF predicted that the majority of HA leaves the joint after ~1-2 days. This quantitative intercompartmental model allows integration of biophysical processes to identify both environmental factors and clinical therapies that affect SF lubricant composition in whole joints.

Interactive Cytokine Regulation of Synoviocyte Lubricant Secretion

“…As transport of HA out of SF occurs through the voids of the synovium extracellular matrix, 8,50 alterations in the tissue structure or in the MW of secreted HA might affect the rate that HA permeates the tissue and is lost from SF. The effect of cytokine-regulated alterations in the size distribution of HA may be magnified by size-dependent retention properties of the synovium, with low MW forms of HA being lost quickly from SF and high MW forms being selectively retained.…”

“…[3][4][5][6] The synthesis rate of these lubricating molecules and the molecular weight (MW) of molecules synthesized are important because the balance between the rate of synthesis and the rate of loss of these molecules, by degradation and transport through the semipermeable synovium, dictates their concentration in SF. 7,8 In naturally occurring or animal models of osteoarthritis (OA), rheumatoid arthritis (RA), and injury, the concentrations of HA and PRG4 in SF are often decreased, as is the MW of HA. [9][10][11][12][13] However, the volume of SF is often increased to an even greater extent, 9,14,15 resulting in an overall increase in lubricant content in SF, and complicating assessments of lubricant production and degradation.…”

Surface Modification with Chemically Modified Synovial Fluid for Flexor Tendon Reconstruction in a Canine Model in Vivo

“…HA, lubricin, and possibly phospholipids are the lubricants in synovial fluid 23,39,40 . Human and animal studies have shown that HA and phospholipids reduce tendon gliding resistance and adhesions, without interfering with tendon healing 18,25,41,42 .…”

The Rationale for Silicon Nitride Bearings in Orthopaedic Applications

“…29 The in vivo environment should be more favorable yet, since human synovial fluid is an excellent lubricant, regardless of the bearing material used. 30,31 Studies on the tribological behavior of ceramics have shown that the wear mechanisms depend on contact conditions during laboratory testing. In most structural ceramics such as silicon nitride, wear occurs through a small-scale surface fracture process if the contact load exceeds a threshold value specific to that material.…”