Early Detection and Intervention Strategies for Acute Cartilage Injury After Intact Joint Impact: In-Vitro Porcine Knee Model

Traumatic injury to cartilage has been shown to lead to Post-traumatic Osteoarthritis (PTOA). The acute phase of PTOA is characterized with increased expression of aggrecanases and inflammatory cytokines in the injured cartilage. Aberrant regulation of microRNAs (miRNAs) in the cartilage has been associated with the pathogenesis of PTOA. The objective of this dissertation work was to elucidate potential early detection and intervention strategies for acute knee injury based on the miRNA and genetic changes of knee joint tissues. An ex-vivo intact joint impact injury model was created to examine the miRNA and inflammatory and degenerative gene expression in cartilage and meniscus during the acute phase of injury. Using this model, four potential early intervention treatments for PTOA were compared, and their effects on the early inflammatory and catabolic events after acute cartilage injury were determined at 8 hours after intact joint impact. The time- and concentration-dependent nature of cellular and extracellular miRNAs in chondrocytes, synoviocytes, and meniscus cells as influenced by inflammatory cytokines and the ratio of extracellular miRNA were analyzed as potential indicator of early OA progression. In a proof of concept study, the ratios of synovial fluid miRNAs after acute cartilage injury were examined using the ex-vivo intact joint impact model as potential indicator of acute cartilage injury. A recommendation for further study is enclosed.

Year	Entry
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Year

Entry

1963

Sokoloff L. Elasticity of articular cartilage: effect of ions and viscous solutions. Science. September 13, 1963;141(3585):1055-1057.

2004

von Porat A, Roos EM, Roos H. High prevalence of osteoarthritis 14 years after an anterior cruciate ligament tear in male soccer players: a study of radiographic and patient relevant outcomes. Ann Rheum Dis. March 2004;63(3):269-273.

1999

Torzilli PA, Grigiene R, Borrelli J Jr, Helfet DL. Effect of impact load on articular cartilage: cell metabolism and viability, and matrix water content. J Biomech Eng. October 1999;121(5):433-441.

2004

Sweigart MA, Zhu CF, Burt DM, deHoll PD, Agrawal CM, Clanton TO, Athanasiou KA. Intraspecies and interspecies comparison of the compressive properties of the medial meniscus. Ann Biomed Eng. November 2004;32(11):1569-1579.

1995

Guilak F, Ratcliffe A, Mow VC. Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study. J Orthop Res. May 1995;13(3):410-421.