HDAC2 interacts with microRNA-503-5p to regulate SGK1 in osteoarthritis

Osteoarthritis (OA) is a disabling joint disease that causes articular cartilage degeneration. It has been implicated that altered expression of histone deacetylase 2 (HDAC2) is found in patients with OA. However, the specific role of HDAC2 in the development of OA still remains enigmatic. Hence, we sought to characterize the functional relevance of HDAC2 in the development of OA.

Anterior cruciate ligament surgery was performed to generate the rat model of OA. Luciferase assay was performed to evaluate the relationship between microRNA-503-5p (miR-503-5p) and serum- and glucocorticoid-inducible kinase-1 (SGK1). Functional experiments were conducted to examine the functional significance of miR-503-5p, histone deacetylase 2 (HDAC2), and SGK1 on the progression of OA by determining proliferation, apoptosis, and expression of apoptosis-associated proteins and inflammatory cytokines.

HDAC2 could inhibit miR-503-5p expression. SGK1 was the target gene of miR-503-5p. Upregulation of miR-503-5p or silencing of HDAC2 contributed to enhanced proliferation, suppressed apoptosis (reduced expression of Caspase-3 and Bax but elevated expression of Bcl2), and promoted inflammation in chondrocytes of OA rats.

In conclusion, our study demonstrated that HDAC2 could promote OA through miR-503-5p/SGK1 axis, which might function as a therapeutic target for OA treatment.