| The theory that the physical changes to the knee joint following anterior cruciate ligament injury, including altered gait kinematics and increased levels of proinflammatory cytokines, may result in cartilage degradation has gained prominence, although the implications of these changes at the tissue and cellular level have received little attention. Thus, the purpose of this thesis was to characterize regional variations in porcine tibial plateau articular cartilage. Three studies were performed to characterize topographical variations in: (1) cartilage matrix content and mechanical properties, (2) chondrocyte gene expression and response to in vitro dynamic compression, and (3) chondrocyte response to the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha).;Biochemical analysis indicated that central regions of the tibial plateau subjected to greater functional loading in vivo were thicker with approximately 50% greater proteoglycan and 35% greater collagen content relative to peripheral regions. Topographical variations in matrix content were paralleled by variations in matrix mechanical properties: the equilibrium Young's Modulus was 490kPa in central region explants and 250kPa in peripheral region explants while the dynamic complex shear modulus (at 0.1 Hz) was 1170kPa in central region explants and 310kPa in peripheral region explants. Consistent with these observations, baseline mRNA levels for type II collagen and aggrecan were approximately twofold greater in central regions compared with peripheral regions of the tibial plateau. In response to in vitro dynamic compression, central region chondrocytes showed greater upregulation of CII and aggrecan than peripheral region cells. Chondrocytes from both regions responded to exogenous TNFalpha with increased expression of matrix degrading enzymes, including matrix metalloproteinases 1, 3, and 13, aggrecanases 1 and 2, and TNFalpha itself. There was significant interaction between TNFalpha and dynamic compression that resulted in a greater upregulation of proteases and TNFalpha than by TNFalpha alone.;These regional variations likely represent adaptation to loading history, and may be important in understanding the fate of cartilage under conditions that cause chronic changes in knee joint loading and biochemistry, such as anterior cruciate ligament injury and meniscectomy, which appear to precede degenerative changes in articular cartilage. |
