MiR-193b modulates osteoarthritis progression through targeting ST3GAL4 via sialylation of CD44 and NF-кB pathway

Abstract

Osteoarthritis (OA) is a worldwide epidemic and debilitating disease. It is urgent to explore the potential molecular mechanisms of OA which has crucial roles in the treatment strategy. As a post-translational modification, sialylation mediates the progression of OA. In current study, differential expression of sialyltransferases (STs) in normal and OA cartilage tissues is detected. The ST3GAL4 expression is significantly increased and positively associated with modified Mankin's score in OA tissue. Alteration of ST3GAL4 respectively mediates the degradation of extracellular mechanisms (ECM), apoptosis and proliferation in chondrocytes. Additionally, miR-193b is identified as a direct regulatory target of ST3GAL4. Functional analysis shows that modulation of ST3GAL4 could be reversed by miR-193b. Over-expression ST3GAL4 modifies CD44 sialylation. Finally, sialylated CD44 reduces the binding capacity to lubricin and mediates the activity of the NF-кB pathway. Collectively, these researches indicate that miR-193b/ST3GAL4 axis impacts OA progression by regulating CD44 sialylation via NF-кB pathway. Our researches propose a precise molecular mechanism and provide a prospective therapeutic target in OA.