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J. Control. Release, Available online 6 February 2023 | https://doi.org/10.1016/j.jconrel.2023.01.071 Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice

Jin-Hyeon Hwang ^a,b,1, Yu-Seong Park ^a,c,1, Hyuk-Soon Kim ^d,1, Dong-ha Kim^a,c, Sang-Hoon Lee ^a, Chan-Hyeong Lee ^c, Seung-Hoon Lee ^c, Jung-Eun Kim^c, Sangkyu Lee ^e, Ho Min Kim ^e, Hyun-Woo Kim ^b, Jihoon Kim ^f, Wonhyo Seo ^g, Hyo-Jung Kwon ^h, Byoung-Joon Song ⁱ, Do-Kyun Kim ^b, Moon-Chang Baek ^c, Young-Eun Cho ^a

^aDepartment of Food and Nutrition, Andong National University, Andong 36729, South Korea
^bKorea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, South Korea
^cDepartment of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, South Korea
^dDepartment of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, South Korea
^eCenter for Biomolecular & Cellular Structure, Institute for Basic Science (IBS), Daejeon 34126, South Korea
^fDivision of Biological Science and Technology, Yonsei University, Wonju 26493, South Korea
^gCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea
^hDepartment of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea
ⁱSection of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA

Corresponding authors: Do-Kyun Kim, Moon-Chang Baek, Young-Eun Cho

Abstract

Plants-releasing exosome-like nanovesicles (PENs) contain miRNA, bioactive lipids, mRNAs, and proteins to exert antioxidant, anti-inflammatory, and regenerative activity. Substances extracted from yams have been reported to promote osteoblast growth in bone regeneration, which prevent weak and brittle bones in osteoporosis. Herein, we describe the beneficial effects of yam-derived exosome-like nanovesicles (YNVs) on promoting differentiation and mineralization of osteoblasts for bone regeneration in ovariectomized (OVX)-induced osteoporotic mice. YNVs were successfully isolated and characterized. YNVs stimulate the proliferation, differentiation, and mineralization of osteoblasts with increased bone differentiation markers (OPN, ALP, and COLI). Interestingly, YNVs do not contain saponins including diosgenin and dioscin known to mainly exert osteogenic activity of yams. Instead, the osteogenic activity of YNVs was revealed to be resulted from activation of the BMP-2/p-p38-dependent Runx2 pathway. As a result, YNVs promote longitudinal bone growth and mineral density of the tibia in the OVX-induced osteoporotic mice in vivo, and these results positively correlate the significant increases in osteoblast-related parameters. In addition, the orally administered YNVs were transported through the GI tract and absorbed through the small intestine. These results showed an excellent systemic biosafety determined by histological analysis and liver/kidney toxicity tests. Taken together, YNVs can serve as a safe and orally effective agent in the treatment of osteoporosis.

논문정보

형식Research article
게재일2023년 02월 (BRIC 등록일 2023-02-15)
연구진국내(교신)+국외 연구진
분야 생명과학 > 영양학

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