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Proteoglycan 4 metabolism and boundary lubrication of articular cartilage

  • Author(s): Schmidt, Tannin A.
  • et al.
Abstract

Articular cartilage is the lubricious, load bearing connective tissue at the end of long bones in synovial joints that normally facilitates low-friction and low-wear articulation via a number of lubrication mechanisms. Boundary lubrication is particularly important for the protection and maintenance of the articular surface, which unfortunately often becomes roughened and eroded in aging and arthritis, with the eventual development of pain and dysfunction. Synovial fluid (SF) contains molecules, such as proteoglycan 4 (PRG4) and hyaluronan (HA), that interact with and adsorb to the articular surface, and are therefore ideally positioned to contribute to boundary lubrication. This dissertation aims to contribute to the understanding of PRG4 metabolism by chondrocytes of the superficial zone of cartilage, and the mechanics of, and contributors to, boundary lubrication of articular cartilage. PRG4 metabolism by chondrocyte subpopulations in various culture systems was regulated differentially by various biochemical stimuli. The phenotype of PRG4 secretion by chondrocytes was generally maintained in that PRG4 was expressed to a much greater degree by chondrocytes from the superficial zone than by those from the middle and deep zones. PRG4 expression and secretion by chondrocytes near the articular surface was highly inhibited by IL-1a and stimulated by TGF-B1, in a dose- dependent manner, in explant cultures of cartilage. An in vitro articular cartilage-on-cartilage boundary lubrication test was implemented and extended to establish conditions where a boundary mode of lubrication was dominant. SF functioned as an effective friction-lowering boundary lubricant, even with a 3-fold decrease in constituent concentration. SF constituents, PRG4 and HA, contributed individually and in combination, both at physiological and pathophysiological concentrations, to the boundary lubrication of apposing articular cartilage surfaces. Collectively these results provide insight into the nature of PRG4 metabolism, the biomechanics of boundary lubrication of articular cartilage, and the role of PRG4, alone and in combination with other putative lubricants. The ability to modulate the dynamic regulation of PRG4, whether in homeostasis or degeneration, may ultimately be useful in prolonging the maintenance or slowing the deterioration of articular cartilage's critical mechanical functions at the end of long bones

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