Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice

Jin-Hyeon Hwang; Yu-Seong Park; Hyuk-Soon Kim; Dong-Ha Kim; Sang-Hoon Lee; Chan-Hyeong Lee; Seung-Hoon Lee; Jung-Eun Kim; Sangkyu Lee; Ho Min Kim; Hyun-Woo Kim; Jihoon Kim; Wonhyo Seo; Hyo-Jung Kwon; Byoung-Joon Song; Do-Kyun Kim; Moon-Chang Baek; Young-Eun Cho

doi:10.1016/j.jconrel.2023.01.071

Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice

J Control Release. 2023 Mar:355:184-198. doi: 10.1016/j.jconrel.2023.01.071. Epub 2023 Feb 6.

Authors

Jin-Hyeon Hwang¹, Yu-Seong Park², Hyuk-Soon Kim³, Dong-Ha Kim², Sang-Hoon Lee⁴, Chan-Hyeong Lee⁵, Seung-Hoon Lee⁵, Jung-Eun Kim⁵, Sangkyu Lee⁶, Ho Min Kim⁶, Hyun-Woo Kim⁷, Jihoon Kim⁸, Wonhyo Seo⁹, Hyo-Jung Kwon¹⁰, Byoung-Joon Song¹¹, Do-Kyun Kim¹², Moon-Chang Baek¹³, Young-Eun Cho¹⁴

Affiliations

¹ Department of Food and Nutrition, Andong National University, Andong 36729, South Korea; Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, South Korea.
² Department of Food and Nutrition, Andong National University, Andong 36729, South Korea; Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, South Korea.
³ Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, South Korea.
⁴ Department of Food and Nutrition, Andong National University, Andong 36729, South Korea.
⁵ Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁶ Center for Biomolecular & Cellular Structure, Institute for Basic Science (IBS), Daejeon 34126, South Korea.
⁷ Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, South Korea.
⁸ Division of Biological Science and Technology, Yonsei University, Wonju 26493, South Korea.
⁹ College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea.
¹⁰ Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea.
¹¹ Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
¹² Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, South Korea. Electronic address: [email protected].
¹³ Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, South Korea. Electronic address: [email protected].
¹⁴ Department of Food and Nutrition, Andong National University, Andong 36729, South Korea. Electronic address: [email protected].

PMID: 36736431
DOI: 10.1016/j.jconrel.2023.01.071

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.

Keywords: Bone mineral density; Exosome-like nanovesicles; Osteoporosis; Yam-derived nanovesicles.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Animals
Cell Differentiation
Dioscorea*
Exosomes* / metabolism
Mice
Osteoblasts / metabolism
Osteogenesis
Osteoporosis* / drug therapy
Osteoporosis* / metabolism
Osteoporosis* / prevention & control