Dr. Lisa Fortier
The broad objective of the studies in this one-year proposal is to investigate the ability of platelet rich plasma (PRP) to modulate an osteoarthritic (OA) environment. PRP is a simple, efficient, and minimally invasive method of obtaining a natural concentration of autologous growth factors and other bioactive molecules to enhance tissue repair, diminish pain, and restore function. For the studies outlined in this proposal, we will take advantage of established synovial fluid and serum markers of OA to evaluate the effects of PRP and hyaluronic acid (HA), the gold standard treatment for OA, on naturally occurring OA tissues.
Our hypothesis for this proposal is that both PRP and HA will significantly and equally decrease biomarkers of pain and loss of glycosaminoglycan from cartilage matrix. We also suspect that PRP will be superior to HA in the capacity to decrease catabolic gene expression and increase anabolic gene expression because of anabolic growth factors contained in PRP. To complete these studies, we will use a co-culture system where synoviocytes and cartilage share a common medium to mimic the native joint environment. Medium in these cultures will be PRP, HA, or control medium. Specific Aim 1 is designed to measure markers of pain in the medium that are associated with pain in patients affected with OA. Using culture medium as a surrogate for synovial fluid, we will used validated ELISAs to measure Substance P, tumor necrosis factor-α (TNF-α), interleukin-15 (IL-15), and IL-1β. We will also quantify the loss of glycosaminoglycan protein using a dye-binding assay. Specific Aim 2 will focus on determining the effects of PRP or HA on biochemical and molecular markers associated with tissue repair and degeneration. In synoviocytes we will use quantitative PCR to measure gene expression of hyaluronic acid and lubricin as anabolic markers, and matrix metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 as catabolic markers. In cartilage, we will measure glycosaminoglycan protein content and using PCR, we will assess anabolic activity through aggrecan, collagen type 2 and lubricin. For cartilage catabolism, we will assay collagen type I, MMP-3, MMP-13 and IL-1β. We have experience with all culture conditions and assays proposed in these experiments and do not anticipate any major obstacles towards completion of our aims.
The expectation is that knowledge gained though the studies outlined in this proposal will provide immediately relevant and clinically applicable information regarding the rational use of PRP in the treatment of OA in horse and human patients. These results should determine if PRP and or HA act to only decrease joint pain or if they also improve the OA environment. A joint treatment to address both pain and joint homeostasis would decrease human and animal discomfort and loss of performance and associated revenue.