53. CARTILAGE AND SYNOVIUM GENE EXPRESSION CHANGES DURING PTOA PROGRESSION

Department: Bioengineering
Faculty Advisor(s): Robert L. Sah

Primary Student
Name: Aimee Rose Raleigh
Email: araleigh@ucsd.edu
Phone: 650-454-0605
Grad Year: 2018

Abstract
Background. Acute injury to the cartilage or the stabilizing structures of the knee, such as the cruciate ligaments and meniscus, is associated with post-traumatic osteoarthritis (PTOA). PTOA has rarely been studied temporally from the acute (1-7 days) to the chronic (>4 weeks) phase of disease progression in an animal model, so the connection between early transient inflammatory signals and joint degeneration is unclear. The interaction between the various cell types present within the joint (including fibroblast-like synoviocytes and chondrocytes) following joint trauma, altered biomechanics, or instability influences the production of pro-inflammatory mediators such as cytokines and proteases that contribute to PTOA progression. Despite previous studies using synovial joint cells in co-culture models, there is no definitive sequence of post-injury paracrine signaling and the subsequent production of joint catabolic, structural, and lubricating molecules. Descriptive gene expression studies can be complemented with an in vitro synovial joint co-culture model to better understand synoviocyte-chondrocyte signaling during PTOA progression. Aim. To measure relative gene expression in synovium and cartilage tissues following ACLT in a rabbit model to track changes in inflammatory, structural, and lubricating molecules over time so that tissue-specific transcriptional changes can provide insight into early predictors of joint degeneration. Methods. A rabbit model of PTOA involving anterior cruciate ligament transection (ACLT) was utilized to destabilize the joint. At 1, 4, 7, 14, 28, and 42 days post-injury (n=6 rabbits per time point), the synovium and cartilage were harvested and real-time quantitative PCR was carried out on 23 genes central to PTOA disease progression. Results. Inflammatory markers were up-regulated with a bimodal pattern of expression over the short (1-7 days) and long (14-42 days) term following ACLT for both regions of cartilage (femoral condyle, tibial plateau) as well as in the synovium. Structural and lubricating molecules demonstrated expression that varied by tissue type and region. Conclusions and Future Work. At these extended time points, it appears that a condition of chronic inflammation is established following acute injury, and this catabolic state has an extended negative effect on the production of structural and lubricating elements necessary for proper joint function. To simplify the complex in vivo environment, a synovial joint bioreactor has been developed to determine how cells in the joint interact and respond to an initial pro-inflammatory stimulus at the transcriptional level in vitro.

Industry Application Area(s)
Life Sciences/Medical Devices & Instruments | Diagnostics

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