UC San Diego

Articular cartilage provides a low-friction, load bearing surface that allows the bones of diarthrodial joints to slide smoothly against each other, with the zonal variations in cartilage matrix structure imparting different functions to each zone. The ability of mechanical stimuli to regulate chondrocyte production of matrix molecules involved in load-bearing has been well documented. Recently it has been suggested that chondrocyte metabolism of specialized molecules secreted by the superficial zone, such as proteoglycan 4, that mediate the lubrication function of the articular surface, may also depend on biomechanical cues. The overall motivation of this dissertation was to contribute to the understanding of the role of biomechanical stimulation in maintaining boundary lubrication of the articular surface by investigating the effects of various loading protocols in vitro (explanted cartilage disks), ex vivo (intact cartilage during whole-joint culture), and in vivo, on PRG4 metabolism and articular surface integrity. In vitro studies demonstrated that static and dynamic compression and dynamic shear stimulation regulate PRG4 biosynthesis, both during loading and after unloading. Similarly, continuous rehabilitative motion applied to whole joints during culture stimulated PRG4 biosynthesis, in a manner dependent on region within the joint, as different regions experienced different loading environments. Marked site- associated variation in cartilage surface integrity was also shown to exist in vivo, likely due to variation in biomechanical environments with joint region. Finally, it was shown that PRG4 molecules can be removed from and re- attached to the articular cartilage surface, which suggests a mechanism by which secreted PRG4 molecules might maintain lubrication function. Elucidating the role of mechanical stimuli, both in vitro and in vivo, in regulating cartilage metabolism of PRG4 and articular surface integrity could lead to an understanding of the processes involved in joint health and degeneration, and possible techniques for tissue-engineering of cartilage tissue with a functional surface layer