Extracellular vesicles from adipose tissue-derived stem cells alleviate osteoporosis through osteoprotegerin and miR-21-5p
- Authors
- Lee, Kyoung Soo; Lee, Jeongmi; Kim, Hark Kyun; Yeom, Seung Ho; Woo, Chang Hee; Jung, Youn Jae; Yun, Ye Eun; Park, So Young; Han, Jihoon; Kim, Eunae; Sul, Jae Hoon; Jung, Jae Min; Park, Jae Hyung; Choi, Ji Suk; Cho, Yong Woo; Jo, Dong-Gyu
- Issue Date
- Oct-2021
- Publisher
- WILEY
- Keywords
- extracellular vesicles; human adipose tissue-derived stem cells; let-7b-5p; miR-21-5p; osteoporosis; osteoprotegerin
- Citation
- JOURNAL OF EXTRACELLULAR VESICLES, v.10, no.12, pp 1 - 18
- Pages
- 18
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF EXTRACELLULAR VESICLES
- Volume
- 10
- Number
- 12
- Start Page
- 1
- End Page
- 18
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/108195
- DOI
- 10.1002/jev2.12152
- ISSN
- 2001-3078
2001-3078
- Abstract
- Osteoporosis is one of the most common skeletal disorders caused by the imbalance between bone formation and resorption, resulting in quantitative loss of bone tissue. Since stem cell-derived extracellular vesicles (EVs) are growing attention as novel cell-free therapeutics that have advantages over parental stem cells, the therapeutic effects of EVs from adipose tissue-derived stem cells (ASGEVs) on osteoporosis pathogenesis were investigated. ASC-EVs were isolated by a multi-filtration system based on the tangential flow filtration (TFF) system and characterized using transmission electron microscopy, dynamic light scattering, zeta potential, flow cytometry, cytokine arrays, and enzyme-linked immunosorbent assay. EVs are rich in growth factors and cytokines related to bone metabolism and mesenchymal stem cell (MSC) migration. In particular, osteoprotegerin (OPG), a natural inhibitor of receptor activator of nuclear factor-xB ligand (RANKL), was highly enriched in ASCEVs. We found that the intravenous administration of ASC-EVs attenuated bone loss in osteoporosis mice. Also, ASC-EVs significantly inhibited osteoclast differentiation of macrophages and promoted the migration of bone marrow-derived MSCs (BM-MSCs). However, OPG-depleted ASC-EVs did not show anti-osteoclastogenesis effects, demonstrating that OPG is critical for the therapeutic effects of ASC-EVs. Additionally, small RNA sequencing data were analysed to identify miRNA candidates related to anti-osteoporosis effects. miR-21-5p in ASG-EVs inhibited osteoclast differentiation through Acvr2a down-regulation. Also, let-7b-5p in ASC-EVs significantly reduced the expression of genes related to osteoclastogenesis. Finally, ASC-EVs reached the bone tissue after they were injected intravenously, and they remained longer. OPG, miR-21-5p, and let-7b-5p in ASC-EVs inhibit osteoclast differentiation and reduce gene expression related to bone resorption, suggesting that ASC-EVs are highly promising as cell-free therapeutic agents for osteoporosis treatment.
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