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Published on: June 25, 2013
Naproxen attenuates osteoarthritis progression through inhibiting the expression of prostaglandinl-endoperoxide
Cuijiang Wang1, Fei Wang1, Fen Lin2
1Department of Pain Management, Linyi People's Hospital, Linyi, Shandong, China.
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.
Insights
Naproxen treatment suppresses prostaglandin-endoperoxide synthase 1 (PTGS1) in osteoarthritis (OA) synovial cells. This reduces OA cell migration and invasion while promoting apoptosis, offering a potential therapeutic strategy for OA.
Area of Science:
- Biomedical research
- Molecular biology
- Pharmacology
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and synovial inflammation.
- Identifying molecular targets for OA treatment is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the therapeutic effects of naproxen on osteoarthritis.
- To identify the biological target of naproxen in OA synovial cells.
Main Methods:
- Messenger RNA microarray analysis to identify differentially expressed genes (DEGs) in OA synovial tissues.
- Weighted gene coexpression network analysis to determine hub genes.
- Quantitative real-time polymerase chain reaction and western blot to validate PTGS1 expression.
- Transwell assays and in vivo mouse models (anterior cruciate ligament transection) to assess cell migration, invasion, and apoptosis.
Main Results:
- Prostaglandin-endoperoxide synthase 1 (PTGS1) was identified as a hub gene overexpressed in OA synovial cells.
- Naproxen treatment significantly downregulated PTGS1 expression in OA synovial cells.
- Naproxen inhibited OA synoviocyte migration and invasion while promoting apoptosis.
- Naproxen influenced the expression of other OA-related genes, including MMP-13 and COX-2.
Conclusions:
- Naproxen effectively suppresses PTGS1 expression in OA synovial cells.
- Naproxen demonstrates therapeutic potential by inhibiting OA synoviocyte migration/invasion and promoting apoptosis.
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