Title page for ETD etd-0404102-114211

Type of Document Dissertation
Author Kim, Dae Young
Author's Email Address dykim@vetmed.lsu.edu
URN etd-0404102-114211
Title Role of Chondrocyte Apoptosis in the Pathogenesis of Equine Osteoarthritis
Degree Doctor of Philosophy (Ph.D.)
Department Agronomy & Environmental Management
Advisory Committee
Advisor Name Title
Doo-Youn Cho Committee Chair
Daniel B. Paulsen Committee Member
H. Wayne Taylor Committee Member
Rustin M. Moore Committee Member
Mary H. Manhein Dean's Representative
  • caspase-3
  • horse
  • hydrostatic pressure
  • osteoarthritis
  • bcl-2
  • chondrocyte
  • apoptosis
Date of Defense 2002-03-12
Availability unrestricted
Osteoarthritis (OA), a non-inflammatory, degenerative disease of articular cartilages, is a common cause of poor performance and early retirement in equine athletes. Pathologically, OA is characterized by matrix degradation and decreased chondrocyte numbers. A mechanical stress is believed to be the major etiologic factor of OA development. Recent studies have indicated that apoptosis is responsible for hypocellularity in OA cartilage and that chondrocyte death by apoptosis could directly contribute to matrix degradation. Increased nitric oxide (NO), a free radical, has been implicated as a cause of chondrocyte apoptosis. No studies, however, have been performed on chondrocyte apoptosis in equine OA. We investigated chondrocyte apoptosis in equine OA cartilage and its relationship to matrix degradation and NO production. Furthermore, we studied whether mechanical stress could induce chondrocyte apoptosis and how NO production and Bcl-2 and caspase-3 proteins contribute to chondrocyte apoptosis by using a novel pressure-loading system. Five OA and three normal equine articular cartilage samples were graded histopathologically and stained with polyclonal nitrotyrosine antibody. Chondrocyte apoptosis was determined by TUNEL assay. For pressure-loading experiment, equine chondrocytes were isolated separately from superficial and deep layers of articular cartilages, embedded in alginate constructs, and intermittently pressurized at 1,000 100 psi (approximately 6.8 0.6 MPa) for 12 hours. TUNEL assay, immunohistochemistry with polyclonal antisera to Bcl-2 and caspase-3, and colorimetric nitrite assay were applied to the chondrocytes that adhered on glass slides by cytospin. Chondrocyte apoptosis occurred much more frequently in equine OA cartilage than in normal cartilage, and was closely correlated with matrix degradation and NO production. The cyclic hydrostatic pressure-treated chondrocytes had a higher percentage of apoptosis than the controls. The pressure-loaded chondrocytes also produced increased NO and expressed elevated Bcl-2 and caspase-3, as compared with the control groups. The present study suggests that pressure-induced NO levels play a critical role in the equine chondrocyte apoptosis process through Bcl-2 and caspase-3 pathways and mechanical stress may contribute to equine OA pathogenesis via chondrocyte apoptosis induced by endogenous NO.
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