1. Academic Validation
  2. Apremilast prevents IL‑17‑induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1

Apremilast prevents IL‑17‑induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1

  • Int J Mol Med. 2021 Mar;47(3):12. doi: 10.3892/ijmm.2021.4845.
Benlong Wang 1 Wei Sun 1 Kunwei Bi 1 Yong Li 1 Feng Li 1
Affiliations

Affiliation

  • 1 Department of Sports Medicine of Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277000, P.R. China.
Abstract

Osteoarthritis is the most prevalent joint degenerative disease and has been considered a major cause of severe joint pain and physical disability in the elderly. The chondrocyte is the only cell type found in articular cartilage and chondrocyte senescence plays a pivotal role in the pathogenesis of osteoarthritis. Apremilast is an oral PDE4 Inhibitor and has been used for the treatment of patients with active psoriatic arthritis. In the present study, the biological function of apremilast was examined in an interleukin (IL)‑17‑treated chondrocyte model. Expression levels of target genes and proteins were measured using reverse transcription‑quantitative PCR, ELISA, and western blotting, respectively. ROS levels in chondrocytes were examined using the Fluorescent Dye DCFH‑DA. Cellular senescence was determined using senescence-associated-β-galactosidase staining. The profile of cell cycle phases was analyzed via flow cytometry. It was revealed that treatment with apremilast reduced the expression of IL‑1β, MCP‑1, and the production of ROS. SA‑β‑gal staining results indicated that the presence of apremilast suppressed IL‑17‑induced cellular senescence. Furthermore, apremilast prevented IL‑17‑induced G0/G1 phase cell cycle arrest. In addition, it was demonstrated that apremilast suppressed IL‑17‑induced expression of p21 and PAI‑1. Notably, the silencing of Sirtuin 1 (SIRT1) abolished the protective effect of apremilast against IL‑17‑induced cellular senescence, suggesting that the action of apremilast in chondrocytes is dependent on SIRT1. In conclusion, the present results revealed that apremilast exerted a beneficial effect, thereby protecting chondrocytes from senescence induced by IL‑17.

Keywords

osteoarthritis; chondrocyte senescence; apremilast; plasminogen activator inhibitor‑1; sirtuin 1.

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