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  2. SP1‑mediated ADAMTS5 transcription promotes IL‑1β‑induced chondrocyte injury via Wnt/β‑catenin pathway in osteoarthritis

SP1‑mediated ADAMTS5 transcription promotes IL‑1β‑induced chondrocyte injury via Wnt/β‑catenin pathway in osteoarthritis

  • Mol Med Rep. 2024 Aug;30(2):149. doi: 10.3892/mmr.2024.13273.
Xiaoting Hao 1 Xiaxia Wu 2
Affiliations

Affiliations

  • 1 Department of Teaching Administration, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China.
  • 2 Department of Radiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China.
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, interleukin‑1β (IL‑1β)‑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), matrix‑related markers and Wnt/β‑catenin pathway‑related 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 transcription‑quantitative PCR, and the interaction between SP1 and ADAMTS5 was analyzed using a dual‑luciferase reporter assay and chromatin immunoprecipitation assay. IL‑1β suppressed proliferation, but promoted Apoptosis, extracellular matrix degradation, inflammation and oxidative stress in chondrocytes. ADAMTS5 was upregulated in IL‑1β‑induced chondrocytes, and its knockdown alleviated IL‑1β‑induced chondrocyte injury. SP1 could bind to the ADAMTS5 promoter region to promote its transcription, and SP1 knockdown relieved IL‑1β‑induced chondrocyte injury by reducing ADAMTS5 expression. The SP1/ADAMTS5 axis activated the Wnt/β‑catenin pathway, and the Wnt/β‑catenin pathway agonist, SKL2001, reversed the protective effect of ADAMTS5 knockdown on chondrocyte injury induced by IL‑1β. 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/β‑catenin pathway.

Keywords

ADAMTS5; Wnt/β‑catenin; interleukin‑1β‑induced chondrocytes; osteoarthritis; specificity protein 1.

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