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

被引：122

作者：

Hwang, Jin-Hyeon ^{[1
,2
]}

Park, Yu-Seong ^{[1
,3
]}

Kim, Hyuk-Soon ^{[4
,5
]}

Dong-ha Kim ^{[1
,3
]}

Lee, Sang-Hoon ^{[1
]}

Lee, Chan-Hyeong ^{[3
]}

Lee, Seung-Hoon ^{[3
]}

Kim, Jung-Eun ^{[3
]}

Lee, Sangkyu ^{[6
]}

Kim, Ho Min ^{[6
]}

Kim, Hyun-Woo ^{[2
]}

Kim, Jihoon ^{[7
]}

Seo, Wonhyo ^{[8
]}

Kwon, Hyo-Jung ^{[9
]}

Song, Byoung-Joon ^{[10
]}

Kim, Do-Kyun ^{[2
]}

Baek, Moon-Chang ^{[3
]}

Cho, Young-Eun ^{[1
]}

机构：

[1] Andong Natl Univ, Dept Food & Nutr, Andong 36729, South Korea

[2] Jeonbuk Natl Univ, Korea Zoonosis Res Inst, Iksan 54531, South Korea

[3] Kyungpook Natl Univ, Sch Med, Dept Mol Med, CMRI, Daegu, South Korea

[4] Dong A Univ, Dept Biomed Sci, Coll Nat Sci, Grad Sch, Busan 49315, South Korea

[5] Dong A Univ, Dept Hlth Sci, Grad Sch, Busan 49315, South Korea

[6] Inst Basic Sci IBS, Ctr Biomol & Cellular Struct, Daejeon 34126, South Korea

[7] Yonsei Univ, Div Biol Sci & Technol, Wonju 26493, South Korea

[8] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea

[9] Chungnam Natl Univ, Coll Vet Med, Dept Vet Pathol, 99 Daehak Ro, Daejeon 34134, South Korea

[10] NIAAA, Sect Mol Pharmacol & Toxicol, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2023年 / 355卷

基金：

新加坡国家研究基金会;

关键词：

Exosome-like nanovesicles; Yam -derived nanovesicles; Bone mineral density; Osteoporosis; ALKALINE-PHOSPHATASE ACTIVITY; ACTIVATED PROTEIN-KINASE; DRUG-DELIVERY; EXTRACELLULAR VESICLES; CELL-DIFFERENTIATION; COLLAGEN-SYNTHESIS; BONE-FORMATION; PROLIFERATION; GROWTH; IDENTIFICATION;

D O I：

10.1016/j.jconrel.2023.01.071

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 COL-I). 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.

引用

页码：184 / 198

页数：15

共 61 条

[31] Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-β and bone morphogenetic protein [J].