SP1mediated ADAMTS5 transcription promotes IL1ßinduced chondrocyte injury via Wnt/ßcatenin pathway in osteoarthritis.
Mol Med Rep
; 30(2)2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38940327
ABSTRACT
Osteoarthritis (OA) is a chronic disease that involves chondrocyte injury. ADAMTS5 has been confirmed to mediate chondrocyte injury and thus regulate OA progression, but its underlying molecular mechanisms remain unclear. In the present study, interleukin1ß (IL1ß)induced chondrocytes were used to mimic OA in vitro. Cell proliferation and apoptosis were assessed by MTT assay, EdU assay and flow cytometry, and protein levels of ADAMTS5, specificity protein 1 (SP1), matrixrelated markers and Wnt/ßcatenin pathwayrelated markers were examined using western blotting. In addition, ELISA was performed to measure the concentrations of inflammation factors, and oxidative stress was evaluated by detecting SOD activity and MDA levels. The mRNA expression levels of ADAMTS5 and SP1 were determined by reverse transcriptionquantitative PCR, and the interaction between SP1 and ADAMTS5 was analyzed using a dualluciferase reporter assay and chromatin immunoprecipitation assay. IL1ß suppressed proliferation, but promoted apoptosis, extracellular matrix degradation, inflammation and oxidative stress in chondrocytes. ADAMTS5 was upregulated in IL1ßinduced chondrocytes, and its knockdown alleviated IL1ßinduced chondrocyte injury. SP1 could bind to the ADAMTS5 promoter region to promote its transcription, and SP1 knockdown relieved IL1ßinduced chondrocyte injury by reducing ADAMTS5 expression. The SP1/ADAMTS5 axis activated the Wnt/ßcatenin pathway, and the Wnt/ßcatenin pathway agonist, SKL2001, reversed the protective effect of ADAMTS5 knockdown on chondrocyte injury induced by IL1ß. To the best of our knowledge, the present study was the first to reveal the interaction between SP1 and ADAMTS5 in OA progression and indicated that the SP1/ADAMTS5 axis mediates OA progression by regulating the Wnt/ßcatenin pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoartritis
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Factor de Transcripción Sp1
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Condrocitos
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Interleucina-1beta
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Vía de Señalización Wnt
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Proteína ADAMTS5
Límite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2024
Tipo del documento:
Article