Characterization of pro-apoptotic and matrix-degradative gene expression following induction of osteoarthritis in mature and aged rabbits
ABSTRACT The genetic and molecular changes leading to the distinctive alterations of aged cartilage and its propensity for developing osteoarthritis (OA) are unknown. We hypothesized that pro-apoptotic and matrix-degradative gene expression in a rabbit model of induced OA using mature and aged animals might elucidate this relationship.
Groups of six mature and aged rabbits underwent anterior cruciate ligament transection (ACLT) and were sacrificed 4 weeks after surgery to create an Outerbridge grade II OA. RNA was extracted from the articular cartilage and menisci of the affected knee and was examined with regard to expression of the following genes: Caspase 8, Fas, Fas ligand (Fas-L), p53, aggrecanase, matrix metalloproteinase (MMP)-1, and MMP-3-MMP-13. A second cohort of mature and aged animals was sacrificed with no intervention to the joint and gene expression was assessed in a similar manner.
Fas and Caspase 8 showed significantly increased expression in the cartilage of mature animals with induced OA when compared to unoperated controls while induction of OA in aged rabbits did not significantly increase expression of any of the apoptosis genes. Among unoperated animals, the aged cohort showed significantly increased expression of MMP-1 and aggrecanase in cartilage when compared to mature animals. MMP-13 expression was upregulated in aged cartilage following induction of OA. Although ACLT animals showed gross thinning and irregularities within the meniscus, only the expression of Caspase 8 in the aged rabbits was significantly increased after induction of OA.
Aging of articular cartilage shares some qualities with the development of OA, as seen in the parallel increases in gene expression of Caspase 8 and Fas. Although this may imply a common mechanism of cartilage degeneration in aging and OA or even a spectrum of disease, both are complex processes requiring further study.
- SourceAvailable from: Kelly J Hendricks
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- "J Clin Exp Med 2011;4(4):285-298 ture to the development of PTOA . Chondrocyte apoptosis may take place soon or more remotely after articular cartilage disruption     . This can occur with or without visible damage to the cartilage . "
ABSTRACT: Osteoarthritis (OA) is characterized by joint pain and stiffness with radiographic evidence of joint space narrowing, osteophytes, and subchondral bone sclerosis. Posttraumatic OA (PTOA) arises from joint trauma, which accounts for a fraction of all patients with OA. Articular cartilage breakdown can occur soon or for years after a joint injury. Even with the current care of joint injuries, such as anatomic reduction and rigid fixation of intra-articular fractures and reconstruction of ruptured ligaments with successful restoration of joint biomechanics, the risk of PTOA after joint injuries ranges from 20% to more than 50%. The time course for the progression of PTOA is highly variable and risk of PTOA increases with patient age at the time of joint injury, suggesting that biologic factors may be involved in the progression of PTOA. Therapeutic options are limited due largely to the lack of information on the mechanisms underlying the progression of PTOA. This review summarizes the current studies on the pathogenetic mechanisms of PTOA, with a main focus on the metabolic changes in articular cartilage in the acute posttraumatic phase and the early chronic phase, a clinically asymptomatic period. Recent studies have revealed that mechanical damage to the articular tissues may lead to changes in gene expression and cartilage metabolism, which could trigger a cascade of events leading to degradation of articular cartilage and pathologic changes in other joint tissues. Understanding the mechanobiologic, molecular and cellular changes that lead to continued cartilage degradation in the relatively early phases after joint injury may open up new opportunities for early clinical intervention.International Journal of Clinical and Experimental Medicine 01/2011; 4(4):285-98. · 1.42 Impact Factor
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ABSTRACT: Soft-switching topologies with inherent ZVS capability are suitable for efficient high frequency operation. One of the widely applied soft switching topologies is the asymmetrical half-bridge converter (AHBC) that has available numerous topological variations developed recently. This paper illustrates an unified model and method of analysis by means of AHBC for three topological versions: two-transformer; integrated magnetics; and current doubler rectifier. This approach allows a comparison between the circuits giving insight into design tradeoffs and permitting optimization for component stress, cost and efficiency. The unified model of AHBC is valid for three possible modes of operation: one CCM and two DCMTelecommunication Energy Conference, 1999. INTELEC '99. The 21st International; 07/1999