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Mitochondrial Transplantation Ameliorates the Development and Progression of Osteoarthritis

  • A Ram Lee (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Jin Seok Woo (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Seon-Yeong Lee (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Hyun Sik Na (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Keun-Hyung Cho (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Yeon Su Lee (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Jeong Su Lee (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Seon Ae Kim (Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea) ;
  • Sung-Hwan Park (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Seok Jung Kim (Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea) ;
  • Mi-La Cho (Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of Korea)
  • Received : 2021.08.18
  • Accepted : 2021.12.27
  • Published : 2022.04.30
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Abstract

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI20C1496).

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