Journal of Marine Bioscience and Biotechnology (한국해양바이오학회지)

The Korean Society for Marine Biotechnology (한국해양바이오학회)
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Fermented extract of Laminaria japonica enhances osteogenic differentiation via autophagy activation in MC3T3-E1 osteoblasts

MC3T3-E1 골아세포에서 자가포식 활성화를 통한 다시마 발효 추출물의 골형성 분화 촉진

  • Nara Jeong (Anti-Aging Research Center, Dong-eui University) ;
  • Hye-Jin Hwang (Anti-Aging Research Center, Dong-eui University) ;
  • Yung Hyun Choi (Anti-Aging Research Center, Dong-eui University)
  • 정나라 (동의대학교 항노화연구소) ;
  • 황혜진 (동의대학교 항노화연구소) ;
  • 최영현 (동의대학교 항노화연구소)
  • Received : 2026.04.28
  • Accepted : 2026.06.19
  • Published : 2026.06.30
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Abstract

Fermented marine resources have emerged as promising functional materials with diverse biological activities. However, their roles in bone metabolism and the underlying mechanisms remain insufficiently understood. In this study, the effects of a fermented extract of sea tangle (Laminaria japonica; FST) on osteogenic differentiation and the involvement of autophagy in MC3T3-E1 pre-osteoblasts were investigated. Under non-cytotoxic conditions, FST significantly enhanced osteogenic differentiation, as evidenced by increased alkaline phosphatase (ALP) activity and mineralized nodule formation under osteogenic growth medium conditions. FST also upregulated the expression of key osteogenic markers, including Runx2, osterix, bone morphogenetic protein-2, and collagen I, and promoted the nuclear localization of Runx2. Notably, FST activated autophagy, as demonstrated by the increased expression of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II and Beclin 1, an increased Cyto-ID-positive cell population, and enhanced LC3 puncta formation. Co-treatment with the autophagy inhibitor 3-methyladenine attenuated FST-induced autophagy and significantly suppressed osteogenic marker expression, ALP activity, and mineralization. These findings indicate that autophagy plays a critical role in mediating FST-induced osteogenic differentiation. In conclusion, FST promotes osteoblast differentiation through autophagy-dependent mechanisms, likely involving the activation of Runx2-mediated transcriptional programs. This study provides novel mechanistic insights into the bone-protective potential of fermented marine-derived resources and suggests that FST is a promising candidate for the development of functional materials targeting bone-related disorders.

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References

  1. Wu, Z., Li, W., Jiang, K., Lin, Z., Qian, C., Wu, M., Xia, Y., Li, N., Zhang, H., Xiao, H., Bai, J., Geng, D. 2024. Regulation of bone homeostasis: signaling path- ways and therapeutic targets. MedComm (2020) 5, e657.
  2. Kim, J. E. 2022. Osteoclastogenesis and osteogenesis. Int. J. Mol. Sci. 23, 6659.
  3. Zhou, T., Yu, Y., Yang, S., Xiao, F., Yu, R., Zhang, G. 2026. Molecular mechanisms and preclinical evidence of natural products in diabetic osteoporosis: a review. Front. Endocrinol. (Lausanne) 17, 1793925.
  4. Zhang, X., Liang, Y., Zhang, F., Liu, X. 2025. Osteoporosis: Molecular pathogenesis and therapeutic interventions. Mol. Biomed. 6, 98.
  5. Han, Y., Kim, D. H., Pack, S. P. 2024. Marine-derived bioactive ingredients in functional foods for aging: Nutritional and therapeutic perspectives. Mar. Drugs 22, 496.
  6. Karthikeyan, A., Joseph, A., Nair, B. G. 2022. Promising bioactive compounds from the marine environment and their potential effects on various diseases. J. Genet. Eng. Biotechnol. 20, 14.
  7. Zhao, F., Cao, M., Wang, B., Jiang, S., Li, J., Aien, T. 2026. Extraction, purification, structure characteristics and biological activities of polysaccharides from Saccharina japonica (Laminaria japonica): A review. Carbohydr. Res. 562, 109826.
  8. Wan, H., Zhang, Y. X., Ga,o Z. C., Shan, G. Y., Liu, F., Li, H. J. 2025. Exploring the potential of fucoidan from Laminaria japonica: A comprehensive review of its biological activities and benefits for human. Int. J. Biol. Macromol. 307, 142297.
  9. Lee, I. S., Ko, S. J., Lee, Y. N., Lee, G., Rahman, H., Kim, B. 2022. The effect of Laminaria japonica on meta- bolic syndrome: A systematic review of its efficacy and mechanism of action. Nutrients 14, 3046.
  10. Piao, M. J., Kang, K. A., Fernando, P. D. S. M., Herath, H. M. U. L., Koh, Y. S., Kang, H. K., Choi, Y. H., Hyun, J. W. 2024. Protective effect of fermented sea tangle extract on skin cell damage caused by particulate matter. Int. J. Med. Sci. 21, 937-948.
  11. Jeong, N., Choi, Y. H. 2023. Fermented sea tangle (Laminaria japonica Aresch) accelerates osteoblast differentiation in murine osteoblastic MC3T3-E1 cells. J. Mar. Biosci. Biotechnol. 15, 24-46.
  12. Choi, W. C., Reid, S. N. S., Ryu, J. K., Kim, Y., Jo, Y. H., Jeon, B. H. 2016. Effects of γ-aminobutyric acid enriched fermented sea tangle (Laminaria japonica) on brain derived neurotrophic factor-related muscle growth and lipolysis in middle aged women. Algae 31, 175–187.
  13. Jang, E. K., Kim, N. Y., Ahn, H. J., Ji, G. E. 2015. γ-aminobutyric acid (GABA) production and angiotensin-I converting enzyme (ACE) inhibitory activity of fermented soybean containing sea tangle by the co-culture of Lactobacillus brevis with Aspergillus oryzae. J. Microbiol. Biotechnol. 25, 1315-1320.
  14. Kang, Y. M., Lee, B. J., Kim, J. I., Nam, B. H., Cha, J. Y., Kim, Y. M., Ahn, C. B., Choi, J. S., Choi, I. S., Je, J. Y. 2012. Antioxidant effects of fermented sea tan- gle (Laminaria japonica) by Lactobacillus brevis BJ20 in individuals with high level of γ-GT: A randomized, double-blind, and placebo-controlled clinical study. Food Chem. Toxicol. 50, 1166-1169.
  15. Moreno-Blas, D., Adell, T., Gonzalez-Estevez, C. 2025. Autophagy in tissue repair and regeneration. Cells 14, 282.
  16. Kao, W. C., Chen, J. C., Liu, P. C., Lu, C. C., Lin, S. Y., Chuang, S. C., Wu, S. C., Chang, L. H., Lee, M. J., Yang, C. D., Lee, T. C., Wang, Y. C., Li, J. Y., Wei, C. W., Chen, C. H. 2022. The role of autophagy in osteoarthritic cartilage. Biomolecules 12, 1357.
  17. Wang, J., Zhang, Y., Cao, J., Wang, Y., Anwar, N., Zhang, Z., Zhang, D., Ma, Y., Xiao, Y., Xiao, L., Wang, X. 2023. The role of autophagy in bone metabolism and clinical significance. Autophagy 19, 2409-2427.
  18. Gomez-Virgilio, L., Silva-Lucero, M. D., Flores-Morelos, D. S., Gallardo-Nieto, J., Lopez-Toledo, G., Abarca-Fernandez, A. M., Zacapala-Gomez, A. E., Luna-Munoz, J., Montiel-Sosa, F., Soto-Rojas, L. O., Pacheco-Herrero, M., Cardenas-Aguayo, M. D. 2022. Autophagy: A key regulator of homeostasis and disease: An overview of molecular mechanisms and modulators. Cells 11, 2262.
  19. Zhu, C., Shen, S., Zhang, S., Huang, M., Zhang, L., Chen, X. 2022. Autophagy in bone remodeling: A regulator of oxidative stress. Front. Endocrinol. (Lausanne) 13, 898634.
  20. Yin, X., Zhou, C., Li, J., Liu, R., Shi, B., Yuan, Q., Zou, S. 2019. Autophagy in bone homeostasis and the onset of osteoporosis. Bone Res. 7, 28.
  21. Qu, Z., Zhao, S., Zhang, Y., Wang, X., Yan, L. 2024. Natural compounds for bone remodeling: Targeting osteoblasts and relevant signaling pathways. Biomed. Pharmacother. 180, 117490.
  22. Zhao, Y., Qu, Z., Zhao, S., Zhang, Y., Gong, Y., Zhang, B., Gao, X., Wang, D., Yan, L. 2023. The potential of natural compounds regulating autophagy in the treatment of osteoporosis. J. Inflamm. Res. 16, 6003-6021.
  23. Li, Z., Li, D., Su, H., Xue, H., Tan, G., Xu, Z. 2022. Autophagy: An important target for natural products in the treatment of bone metabolic diseases. Front. Pharmacol. 13, 999017.
  24. Zhu, S., Chen, W., Masson, A., Li, Y. P. 2024. Cell signaling and transcriptional regulation of osteoblast lin- eage commitment, differentiation, bone formation, and homeostasis. Cell Discov. 10, 71.
  25. Adelipour, M., Saleth, L. R., Ghavami, S., Alagarsamy, K. N., Dhingra, S., Allameh, A. 2022. The role of autophagy in the metabolism and differentiation of stem cells. Biochim. Biophys. Acta Mol. Basis Dis. 1868, 166412.
  26. Perrotta, C., Cattaneo, M. G., Molteni, R., De Palma, C. 2020. Autophagy in the regulation of tissue differ- entiation and homeostasis. Front. Cell Dev. Biol. 8, 602901.
  27. Puissant, A., Fenouille, N., Auberger, P. 2012. When autophagy meets cancer through p62/SQSTM1. Am. J. Cancer Res. 2, 397-413.
  28. Komatsu, M., Ichimura, Y. 2010. Physiological sig- nificance of selective degradation of p62 by autophagy. FEBS Lett. 584, 1374-1378.