The degradation of articular cartilage in Osteoarthritis (OA) is the final result of a futile repair process. The goal of the two projects proposed in Program II """"""""Articular Cartilage Repair: Response to Injury"""""""" is to understand the potential of articular cartilage to repair and identify mechanisms and components which foster successful repair. Project 3 will investigate the potential of articular cartilage to repair in an in vivo animal model following a proteolytic insult. Inherent in the design of animal studies in vivo is the difficulty of separating the effects of biomechanical factors, systemic factors and complex tissue interactions on the cellular response. Therefore, project 4 will evaluate tissue repair in organ culture in vitro, thereby eliminating the biomechanical and systemic effects on the cellular response. First, cartilage will be damaged in vivo with purified enzymes of defined specificity, i.e. chymopapain or collagenase. The tissue will be transferred to organ culture and the repair of the tissue followed ex vivo. Second, the cartilage tissue will be damaged using the same enzymes in vitro and the potential of the tissue to repair in organ culture will be evaluated. Third, cartilage tissue will be damaged by a mixture of proteases derived from cartilage after incubation with specific fibronectin fragments (Fn-f). This should represent a more """"""""physiological"""""""" insult than the purified enzymes described above. Finally, successful cartilage repair may be dependent on the stability of the chondrocyte phenotype. The modulation of the chondrocyte phenotype to a """"""""less differentiated"""""""" cell or a """"""""more mature"""""""" hypertrophic chondrocyte will be evaluated by biochemical methods since such phenotypic alterations would interfere with effective cartilage repair. The greatest advantage of these organ culture experiments is the ability of the """"""""closed"""""""" system to retain all of its components and simplify the measurement of changes in different macromolecules.
| Knudson, Warren; Ishizuka, Shinya; Terabe, Kenya et al. (2018) The pericellular hyaluronan of articular chondrocytes. Matrix Biol : |
| Tezcan, Mehmet E; Goker, Berna; Lidtke, Roy et al. (2017) Long-term effects of lateral wedge orthotics on hip and ankle joint space widths. Gait Posture 51:36-40 |
| Patchigolla, R Krishna R; Knudson, Warren; Schmid, Thomas M (2012) Matrix metalloproteinase-9 in a unique proteoglycan form in avian embryonic growth plate cartilage. Arch Biochem Biophys 520:42-50 |
| Anderson, Donald D; Chubinskaya, Susan; Guilak, Farshid et al. (2011) Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res 29:802-9 |
| Morris, Kirsten J; Cs-Szabo, Gabriella; Cole, Ada A (2010) Characterization of TIMP-3 in human articular talar cartilage. Connect Tissue Res 51:478-90 |
| Rolauffs, Bernd; Muehleman, Carol; Li, Jun et al. (2010) Vulnerability of the superficial zone of immature articular cartilage to compressive injury. Arthritis Rheum 62:3016-27 |
| Farlow, E C; Vercillo, M S; Coon, J S et al. (2010) A multi-analyte serum test for the detection of non-small cell lung cancer. Br J Cancer 103:1221-8 |
| Shakoor, Najia; Sengupta, Mondira; Foucher, Kharma C et al. (2010) Effects of common footwear on joint loading in osteoarthritis of the knee. Arthritis Care Res (Hoboken) 62:917-23 |
| Iacob, Stanca; Cs-Szabo, Gabriella (2010) Biglycan regulates the expression of EGF receptors through EGF signaling pathways in human articular chondrocytes. Connect Tissue Res 51:347-58 |
| Rolauffs, Bernd; Williams, James M; Aurich, Matthias et al. (2010) Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis. Arthritis Rheum 62:489-98 |
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