FOXM1 activates JAK1/STAT3 pathway in human osteoarthritis cartilage cell inflammatory reaction
| Autor: | Xiaohui Lu, Runming Zeng, Zewa Liu, Jiezhuang Fang, Jing Lin, Wanting Zeng, Zhijie Ron |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cartilage
Articular Lipopolysaccharides STAT3 Transcription Factor Pathology medicine.medical_specialty Pyridines Cell Arthritis Inflammation Osteoarthritis General Biochemistry Genetics and Molecular Biology Chondrocytes medicine Humans Pyrroles Gene Silencing Phosphorylation STAT3 Cells Cultured Original Research biology Triazines business.industry Cartilage Forkhead Box Protein M1 Janus Kinase 1 Tyrphostins medicine.disease medicine.anatomical_structure Subchondral bone FOXM1 biology.protein medicine.symptom business Protein Binding Signal Transduction |
| Zdroj: | Exp Biol Med (Maywood) |
| ISSN: | 1535-3699 1535-3702 |
| DOI: | 10.1177/1535370220974933 |
| Popis: | Osteoarthritis (OA), the most prevalent form of arthritis disease, is characterized by destruction of articular cartilage, osteophyte development, and sclerosis of subchondral bone. Transcription factors Janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) and Forkhead box M1 (FOXM1) are key mediators of this inflammatory reaction. In this study, we investigated the interaction between JAK1/STAT3 and FOXM1 in OA. Inflammation is related to the cartilage damage, and lipopolysaccharides (LPS) are a major pro-inflammatory inducer, so LPS was utilized to stimulate chondrocytes and establish a cell-based OA model. We found LPS treatment caused a generation of inflammatory cell factors (IL-1β, IL-6, and TNF-α), and upregulation of inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2) and other inflammatory mediators. Cell viability of chondrocytes was impaired with LPS stimulation, along with an upregulation of JAK1 expression, and phosphorylation and nuclear accumulation of STAT3. The administration of STAT3 inhibitor WP1066, which abated activation and nuclear location of STAT3, depleted the effect of LPS on inflammation and cell death. Co-immunoprecipitation showed that STAT3 was able to bind to FOXM1, and deactivation of STAT3 resulted in the downregulation of FOXM1. Moreover, FOXM1 silencing inhibited the generation of inflammatory cytokines induced by LPS, and the attenuation of cell survival. These findings indicated that the interaction between JAK1/STAT3 and FOXM1 may play a key role in OA pathogenic studies, and suggest the JAK1/STAT3 pathway may be a potential target for OA therapy. |
| Databáze: | OpenAIRE |
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