Naproxen attenuates osteoarthritis progression through inhibiting the expression of prostaglandinl-endoperoxide synthase 1.

OBJECTIVE: This study aims to test the effect of naproxen treatment and the biological target of naproxen for treating osteoarthritis (OA).

METHODS: Differentially expressed genes (DEGs) in OA synovial tissues and normal counterparts were analyzed by messenger RNA microarray analysis. R package (weighted gene coexpression network analysis) was used to divide DEGs into several modules and determine the hub genes in each module. The expression level of prostaglandin-endoperoxide synthase 1 ( PTGS1) in OA synovial cells and tissues was verified by a quantitative real-time polymerase chain reaction and western blot. Transwell assay evaluated the numbers of cell migration and invasion. Furthermore, Safranin O and fast green staining and hematoxylin and eosin staining were performed on joints from anterior cruciate ligament transection mice.

RESULTS: Microarray analysis determined PTGS1 was the hub gene in the black module, which was overexpressed in OA synovial cells and tissues compared with normal synovial cells. OA synovial cells transfected with sh-PTGS1 showed downregulation of PTGS1. After treatment with naproxen, the expression of PTGS1 sharply decreased in the OA group. The migration and invasion of OA synovial cells increased, whereas the cell apoptosis rate decreased when PTGS1 was overexpressed. However, the cell migration and invasion decreased, whereas cells apoptosis increased when it was treated with naproxen. Naproxen could also influence the expression level of six OA-related genes: LUBRICIN, matrix metalloproteinase 13 (MMP-13), cyclooxygenase-2 (COX-2), ACAN, COL2A1, and COL1A1.

CONCLUSION: We validated that naproxen could suppress the expression of PTGS1 in synovial cells. Moreover, naproxen could inhibit the migration/invasion ability of OA synoviocytes and promote the apoptosis rate OA synoviocytes.