2. Academic Validation
  3. Ruscogenin attenuates osteoarthritis by modulating oxidative stress-mediated macrophage reprogramming via directly targeting Sirt3

Ruscogenin attenuates osteoarthritis by modulating oxidative stress-mediated macrophage reprogramming via directly targeting Sirt3

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113336. doi: 10.1016/j.intimp.2024.113336.
Yang Liu 1,  Wenwei Li 2,  Hao Tang 3,  Zhichao Yang 2,  Ming Wei 2,  Wei Zhou 4,  Zheng Li 5,  Wei Huang 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China; Graduate School, Bengbu Medical University, Bengbu 233000, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China.
  • 3 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230001, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China. Electronic address: 734366239@qq.com.
  • 5 Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China. Electronic address: 1042218731@qq.com.
  • 6 Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China. Electronic address: zgkdhwei@ustc.edu.cn.
PMID: 39378655 DOI: 10.1016/j.intimp.2024.113336
Abstract

Background: Synovial inflammation, Cartilage erosion, and subchondral osteosclerosis, which are collectively referred to as the triad of pathogenesis, contribute to osteoarthritis (OA) progression. Specifically, the M1 macrophage in the synovium worsens the development of the illness and is a significant factor in the deterioration and functioning of cartilage.

Objective: To investigate whether Ruscogenin attenuates progressive degeneration of articular cartilage in rats with anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA) by modulating macrophage reprogramming and to explore its specific mechanism of action.

Methods: In vitro, SW1353 cells and RAW264.7 cells were applied to elucidate the mechanisms by which Ruscogenin protects articular cartilage. Specifically, the expression levels of molecules related to cartilage ECM synthesis and degradation Enzymes and macrophages were analysed. In vivo, a rat osteoarthritis model was established using ACLT. The protective effect of Ruscogenin on articular cartilage was observed.

Results: Ruscogenin significantly reversed LPS-induced macrophage inflammatory response and promoted cartilage regeneration-related factors. In addition, Ruscogenin had a significant protective effect on the knee joint of ACLT rats, effectively preventing cartilage degeneration. These positive therapeutic effects were achieved on the one hand by Ruscogenin regulating macrophage reprogramming by targeting SIRT3, and on the Other hand Ruscogenin could attenuate the ROS level of chondrocytes thereby inhibiting chondrocyte Ferroptosis.

Conclusions: Ruscogenin exerts chondroprotective effects by regulating macrophage reprogramming and inhibiting chondrocyte Ferroptosis.

Keywords

Chondrocytes; Ferroptosis; Macrophages; Osteoarthritis; Oxidative stress; Ruscogenin.

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