Plant homeodomain finger protein 23 inhibits autophagy and promotes apoptosis of chondrocytes in osteoarthritis.

BACKGROUND

Plant homeodomain finger protein 23 (PHF23) is a novel autophagy inhibitor gene that has been few studied with respect to orthopedics. This study was to investigate the expression of PHF23 in articular cartilage and synovial tissue, and analyze the relationship between PHF23 and chondrocyte autophagy in osteoarthritis (OA).

METHODS

Immunohistochemical staining and western blot were applied to show the expression of PHF23 in cartilage of different outbridge grades and synovial tissue of patient with OA and healthy control. The normal human chondrocyte pre-treated with rapamycin or 3-methyladenine, treated with interleukin-1β (IL-1β). IL-1β induced expression level of PHF23 and autophagy-related proteins light chain 3B-I (LC3B-I), LC3B-II, and P62, were examined by Western blot. A PHF23 gene knock-down model was constructed with small interfering RNA. Western blot was performed to detect the efficiency of PHF23 and the impact of PHF23 knockout on IL-1β-induced expression of autophagy-related and apoptotic-related proteins in chondrocyte.

RESULTS

The expression of PHF23 was significantly increased in the high-grade cartilage and synovial tissue of patients with OA. The IL-1β-induced expression of PHF23 was gradually enhanced with time. The level of LC3B-II, P62 changed with time. After knockdown of PHF23, the level of autophagy-related proteins increased and apoptotic-related proteins decreased in IL-1β-induced OA-like chondrocytes.

CONCLUSIONS

The expression of PHF23 increased in human OA cartilage and synovium, and was induced by IL-1β through inflammatory stress. PHF23 can suppress autophagy of chondrocytes, and accelerate apoptosis.