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Boundary Mode Frictional Properties of Articular Cartilage: Functional Implications of Lubricin Localization
Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin, a synovial glycoprotein shown to be a boundary lubricant. It is unclear how lubricin boundary lubricates a wide range of bearings from tissue to artificial surfaces, and if the mechanism is similar for soluble and bound lubricin. The objective of this research was to investigate lubricin as a mediator of articular cartilage boundary mode frictional properties. The central hypothesis of this dissertation was that the boundary mode friction coefficient is mediated by localization of lubricin at the tissue surface. In order to determine the frictional properties of cartilage, a linearly oscillating cartilage-on-glass friction apparatus was designed and validated, and a novel extension of the Stribeck curve, a "Stribeck surface," was created to map cartilage lubrication modes. The first aim identified the ability of exogenous lubricin to lubricate articular cartilage and characterized the differential roles of bound and soluble lubricin. The second aim investigated the ability of endogenously synthesized lubricin to lubricate cell-alginate constructs generated from chondrocytes, meniscal fibrochondrocytes, and mesenchymal stem cells. The last aim determined the functional effects of short term exposure to TGF-beta, IL-1beta, and OSM on the frictional properties of cartilage explants. These studies demonstrate that molecular modification of the tissue surface by localization or removal of lubricin altered the boundary mode frictional properties of cartilage. Additionally, localization of lubricin at the tissue surface is not a simple adsorption mechanism, with aggregation, steric arrangement of the molecule, and electrostatic interactions possibly playing a role in lubricin's boundary lubricating ability. These findings point to two distinct mechanisms by which lubricin lubricates, one mechanism involving lubricin bound to the tissue surface and the other involving lubricin in solution. The results presented herein suggest that production of extracellular matrix capable of localizing lubricin may be just as or more important than lubricin production in the lubrication of engineered tissues. Further, the recovery of lubrication for catabolically exposed tissue by exogenous lubricin may be therapeutically important to combat high tissue friction found in injury and disease.
Cartilage lubrication; Cartilage friction; Lubricin; PRG4; TGF-beta; IL-1; OSM; Tissue engineering; mesenchymal stem cells; chondrocytes; cartialge; meniscus
dissertation or thesis