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Vitamin D Attenuates Pain and Cartilage Destruction in OA Animals via Enhancing Autophagic Flux and Attenuating Inflammatory Cell Death

  • JooYeon Jhun (Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Jin Seok Woo (Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Ji Ye Kwon (Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Hyun Sik Na (Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea) ;
  • Keun-Hyung Cho (Rheumatism Research Center, 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) ;
  • Seok Jung Kim (Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea) ;
  • Su-Jin Moon (Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Sung-Hwan Park (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Mi-La Cho (Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea)
  • Received : 2021.12.14
  • Accepted : 2022.04.10
  • Published : 2022.08.31
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Abstract

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)2D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number NRF-2015R1D1A1A01057065 and 2020R1I1A1A01072520).

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