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DUSP4 alleviates LPS-induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway
1Department of Sports Medicine, Ganzhou People's Hospital, Zhanggong, Jiangxi 341000, P.R. China.
Abstract:
Knee osteoarthritis (KOA) is characterized by cartilage damage, and the associated pathogenesis is complex. The expression of dual specificity protein phosphatase 4 (DUSP4) is significantly decreased in osteoarthritis (OA); however, the specific role and mechanism underlying DUSP4 in OA are yet to be elucidated. ATDC5 cells were treated with lipopolysaccharide (LPS) to establish the cell injury model. The expression levels of DUSP4 were decreased in OA chondrocytes, demonstrated by reverse transcription-quantitative PCR and western blot analysis. Following overexpression of DUSP4 by cell transfection, Cell Counting Kit-8, ELISA, TUNEL and western blotting assays were used to detect the cell viability, oxidative stress, inflammation and apoptosis levels of LPS-induced ATDC5 cells. Overexpression of DUSP4 inhibited the activation of the MAPK signaling pathway, thereby reducing oxidative stress levels, inflammatory response and apoptosis in the OA cell model. The mechanisms underlying DUSP4 in OA were further explored following the addition of MAPK signaling pathway agonist, phorbol 12-myristate 13-acetate (PMA). The addition of PMA reversed the inhibitory effects of DUSP4 overexpression on oxidative stress, inflammatory response and apoptosis in cells. In summary, DUSP4 alleviated LPS-induced chondrocyte injury in KOA via the MAPK signaling pathway.
Insights
Dual specificity protein phosphatase 4 (DUSP4) is decreased in knee osteoarthritis (KOA). Overexpressing DUSP4 protects chondrocytes from injury by inhibiting the MAPK pathway, reducing inflammation and apoptosis.
Area of Science:
- Biomedical research
- Cell biology
- Molecular mechanisms of disease
Background:
- Knee osteoarthritis (KOA) involves complex cartilage damage pathogenesis.
- Dual specificity protein phosphatase 4 (DUSP4) expression is reduced in osteoarthritis (OA).
- The precise function and mechanism of DUSP4 in OA remain unclear.
Purpose of the Study:
- To investigate the role and mechanism of DUSP4 in knee osteoarthritis.
- To determine if DUSP4 affects chondrocyte viability, oxidative stress, inflammation, and apoptosis.
- To elucidate the involvement of the MAPK signaling pathway in DUSP4's function in OA.
Main Methods:
- Established an OA cell injury model using ATDC5 cells treated with lipopolysaccharide (LPS).
- Quantified DUSP4 expression using reverse transcription-quantitative PCR and western blot.
- Assessed cell viability, oxidative stress, inflammation, and apoptosis via Cell Counting Kit-8, ELISA, TUNEL, and western blotting assays.
- Investigated the MAPK pathway's role using a specific agonist (PMA).
Main Results:
- DUSP4 expression was significantly decreased in OA chondrocytes.
- Overexpression of DUSP4 inhibited LPS-induced chondrocyte injury.
- DUSP4 overexpression suppressed the MAPK signaling pathway, reducing oxidative stress, inflammation, and apoptosis.
- MAPK pathway activation reversed the protective effects of DUSP4.
Conclusions:
- DUSP4 plays a protective role in knee osteoarthritis.
- DUSP4 alleviates LPS-induced chondrocyte injury in KOA.
- The protective mechanism involves the inhibition of the MAPK signaling pathway.
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