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  2. Cuprorivaite microspheres inhibit cuproptosis and oxidative stress in osteoarthritis via Wnt/β-catenin pathway

Cuprorivaite microspheres inhibit cuproptosis and oxidative stress in osteoarthritis via Wnt/β-catenin pathway

  • Mater Today Bio. 2024 Oct 16:29:101300. doi: 10.1016/j.mtbio.2024.101300.
Bo Li 1 Tongmeng Jiang 2 3 Juan Wang 3 4 Hongping Ge 5 6 Yaqi Zhang 1 Tong Li 1 Chen Wang 5 Weiguo Wang 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, China-Japan Friendship Hospital, Beijing 100029, China.
  • 2 Key Laboratory of Emergency and Trauma of Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou 571199, China.
  • 3 Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, College of Emergency and Trauma, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China.
  • 4 Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province, Hainan Provincial Stem Cell Research Institute, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, 571199, China.
  • 5 Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China.
  • 6 Department of Dermatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Abstract

This study aims to evaluate the therapeutic potential of cuprorivaite microspheres for osteoarthritis (OA), in particular, potential molecular mechanisms were investigated. The microspheres were developed from CA(NO3)2•4H2O, Cu(NO3)2•3H2O, and silica gel, and further therapeutic effects were tested in vitro on mouse primary chondrocytes treated with interleukin-1β (IL-1β) to mimic OA, and in vivo on OA mice induced via anterior cruciate ligament transection (ACLT) surgery. The microspheres were shown to mitigate IL-1β-induced apoptotic, inflammatory, oxidative stress and Cuproptosis markers while enhancing cell viability and extracellular matrix (ECM) components in chondrocytes. Moreover, the microspheres ameliorated histopathological damage, reduced inflammatory, oxidative stress and Cuproptosis markers, and enhanced ECM biomarker levels in OA mice, implicating their role in suppressing Cuproptosis and oxidative stress. The aforementioned effects of the cuprorivaite microspheres were demonstrated by using SKL2001, an agonist of the Wnt/β-catenin pathway. The results suggest cuprorivaite microspheres as a promising intervention for OA and cartilage regeneration, highlighting their therapeutic effects on cellular and molecular levels.

Keywords

Cuproptosis; Cuprorivaite microspheres; Osteoarthritis; Oxidative stress; Wnt/β-catenin pathway.

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