UC San Diego

Articulation (shear and sliding) has been increasingly studied during the last two decades with the realization of its substantial involvement in daily locomotion of the human knee joint. Conventional biological responses of mechanical stimulation on chondrocyte viability has been studied for shear and sliding; but in addition, the close relationship between articulation and lubrication has emphasized the importance of cell-mediated expression of the key boundary lubricating protein proteoglycan 4 (PRG4). While, in the absent of lubrication, shear and sliding between abnormal congruency between joint surfaces can initiate spatially-varied early degeneration, both instantly by direct mechanical damage of the cartilage and through time by mechanobiology. Thus, the overall motivation of this dissertation was to understand the effect of articulation (shear and sliding) on maintaining joint health as well as causing early or progressed degeneration in human articular cartilage.

Spatially-oriented histopathological features were identified in cartilage lesions of human knee medial femoral condyles (MFCs) using a standardized, reliable grading system developed from primary literature, supporting the concept of mechanical articulation-driven cartilage deterioration. To recapitulate in vivo effects of articulation on human articular cartilage, human cartilage explants were subjected to mid to high amplitudes of articulation that can potentially stimulate chondrocyte response and cause matrix damage. Although articulation on cartilage explants induced superficial zone cell death and apoptosis (regardless of aging), only young and not old cartilage responded by secreting higher levels of PRG4 lubricant and continuously expressed enhanced levels of autophagy. However, the articulation regime applied in the absence of lubrication was insufficient to generate noticeable wear at the cartilage surface.

Elucidating the mechanobiology of early degeneration in human articular cartilage by assessing the effects of articulation (shear and sliding) on SZ chondrocyte response and the initiation of matrix damage is one step towards a systems-based understanding of synovial joint homeostasis and derangement in health, aging, and disease. Furthermore, understanding the mechanobiological environments that can initiate cartilage degeneration can be critical to the development of preventive therapies for osteoarthritis.