The Role of TRAPPC9 in Osteoarthritis

Osteoarthritis (OA) is the most prevalent joint disease worldwide, causing chronic disability in older people. The articular cartilage cells, chondrocytes, are responsible for maintaining homeostasis of the ECM by producing its major components. Several activators (pro-inflammatory mediators) such as Interleukin 1 beta (IL-1β) can activate NF-kB signaling pathways. There are two distinct pathways, which can activate the NF-kB signaling cascades. The first one termed canonical pathway, activation of IKKα/IKKβ/IKKg-NEMO complex will activate this pathway. On the other hand, the non-canonical pathway activation relies on NF-kB-inducing kinase (NIK). Trafficking Protein Particle Complex 9 (TRAPPC9) is a major subunit of TRAPPII Complex. Our data showed that TRAPPC9 binds IKKβ and NIK in chondrocytes. We believe such interaction could lead to a potential regulatory role of TRAPPC9 during NF-kB signaling cascades. To explore the role of TRAPPC9 in OA in vitro, first, we measured the gene expression/protein level in normal vs. osteoarthritic condition of human cartilage. Interestingly, TRAPPC9 gene expression/protein level was decreased in IL-1β treated chondrocytes. Next, we determined the effect of TRAPPC9 overexpression using a viral system. TRAPPC9 overexpression might lead to positive or negative regulation of NF-kB signaling cascades. Studies are underway to determine the effects of modulating TRAPPC9 using in vivo studies, which include injection of viral particles of TRAPPC9 overexpression into the knee articular cartilage of C57BL6 mice after OA is surgically induced (DMM model). Collectively, these studies are the first to report a novel role of TRAPPC9 in OA