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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Activation of Nrf2 by sulfuretin stimulates chondrocyte differentiation and increases bone lengths in zebrafish

  • Seo-Hyuk Chang (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Hoi-Khoanh Giong (Microbiome Convergence Research Center, KRIBB) ;
  • Da-Young Kim (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Suji Kim (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Seungjun Oh (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Ui Jeong Yun (Department of Chemical and Biological Engineering, School of Living and Environmental Engineering, Dongyang Mirae University) ;
  • Jeong-Soo Lee (Microbiome Convergence Research Center, KRIBB) ;
  • Kye Won Park (Department of Food Science and Biotechnology, Sungkyunkwan University)
  • Received : 2023.04.14
  • Accepted : 2023.05.22
  • Published : 2023.09.30
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Abstract

Elongation of most bones occur at the growth plate through endochondral ossification in postnatal mammals. The maturation of chondrocyte is a crucial factor in longitudinal bone growth, which is regulated by a complex network of paracrine and endocrine signaling pathways. Here, we show that a phytochemical sulfuretin can stimulate hypertrophic chondrocyte differentiation in vitro and in vivo. We found that sulfuretin stabilized nuclear factor (erythroid-derived 2)-like 2 (Nrf2), stimulated its transcriptional activity, and induced expression of its target genes. Sulfuretin treatment resulted in an increase in body length of zebrafish larvae and induced the expression of chondrocyte markers. Consistently, a clinically available Nrf2 activator, dimethyl fumarate (DMF), induced the expression of hypertrophic chondrocyte markers and increased the body length of zebrafish. Importantly, we found that chondrocyte gene expression in cell culture and skeletal growth in zebrafish stimulated by sulfuretin were significantly abrogated by Nrf2 depletion, suggesting that such stimulatory effects of sulfuretin were dependent on Nrf2, at least in part. Taken together, these data show that sulfuretin has a potential use as supporting ingredients for enhancing bone growth.

Keywords

Acknowledgement

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (NRF-2020R1A2B5B02001592 to K.W.P., NRF-2020R1I1A1A01074938 to U.J.Y., and NRF-2022R1I1A2071529 to J.-S.L.). This study was also partly supported by KRIBB Research Initiative Program (KGM5352322, KGM2112335, KGM9992312, KGM1382312) to J.-S.L.

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