Investigation of molecular mechanism of UCMA in osteoarthritis

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. The identification of novel therapeutic agents and molecular targets are crucially needed for the treatment and prevention of OA. UCMA is a vitamin K-dependent protein. Along with the fact that the exact molecular function of UCMA is still unknown, it is suggested in the current studies that it can be related to the inflammation and calcification processes. In this present study, we investigated the molecular mechanism of UCMA in OA. We showed the relationship of UCMA with the OA-related genes by using an osteoblast cell line, called hFOB1.19, induced with IL-1β. In our study, the expression levels of 16 genes were analyzed with real-time PCR method. The protein levels of UCMA were measured with the Western Blot method. Besides, MMP1, IL-17 and OPG protein levels in the supernatants of cell lines were analyzed with ELISA. In our in vitro OA model, we observed a significant increase in the expression levels of MGP and UTS2 which can be novel therapeutic targets, like UCMA. In our study, we established that IL-1β triggers the main transcription factors (RUNX2 ve OSX) playing role during bone formation and UCMA can be associated with these factors. We showed for the first time that, there is a positive correlation between UCMA and several genes playing role in OA progression and the most affected gene from OA is UCMA. In addition, during IL-1β-induced apoptosis mediated through caspase-3, -8 and -9 pathway in hFOB1.19 cell line, we assessed a significant increase in UCMA expression levels. Besides MMP1 and OPG secretions increased significantly compared to control group. The findings in our study may suggest that, UCMA involves in osteoblast differentiation, bone formation, OA progression, and osteoblast apoptosis. In conclusion, our study provides good evidence about the potential value of UCMA in the pathophysiology of OA and shows that UCMA is a promising molecular target to develop therapeutic approaches against OA.