Studies in our laboratories and the laboratories of others have now indicated that the avascular portion of the fibrocartilaginous knee join meniscus has the potential to repair itself. The experiments described in this application are designed to study further the biology and repair capabilities of the knee joint meniscus, and provide important data regarding fundamental aspects of the cell biology of meniscal fibrocartilage. The specific aims of the project are to: (1) determine, using cell culture and our recently developed organ culture model, the role played by synoviocytes and several interrelated physiologic compounds in meniscal wound repair; and (2) develop a parallel in vivo animal model to study meniscal wound repair based on the results of the first specific aim. To achieve these goals, the following methodologies will be used: (1) cell and organ culture techniques; (2) histological techniques, to include light and electron microscopy; (3) conventional and high-pressure liquid chromatography; (4) cytoplasmic dot blot hybridization using specific cDNA probes; (5) autoradiography; (6) morphometry; and (7) immunohistochemistry. Data obtained from the proposed experiments will provide a basis for future practical application to clinical orthopaedic practice. Further development and refining of our meniscal organ culture system will allow for the future screening of the effects of drugs and other compounds on the response of meniscal tissue to injury. Ultimately, the in vivo animal models may pave the way for human trials in an effort to obviate the need for meniscectomies and their morbid sequelae. Both the in vitro and in vivo models will be useful for future studies designed to study the biomechanical properties of the repair tissue as well as design of a synthetic biomatrix to expedite meniscal wound repair. Thus, insights gained from the proposed research can be expected to futher our understanding of synovial joint physiology and thereby aid in the design and selection of treatment modalities to be used by the clinicians.