PMID- 38017286
OWN - NLM
STAT- Publisher
LR  - 20231128
IS  - 1573-4927 (Electronic)
IS  - 0006-2928 (Linking)
DP  - 2023 Nov 29
TI  - Extracellular Vesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells 
      Suppress RANKL-Induced Osteoclast Differentiation via miR122-5p.
LID - 10.1007/s10528-023-10569-5 [doi]
AB  - Researchers are increasingly interested in cell therapy using mesenchymal stem 
      cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. 
      Thus, we isolated and characterized extracellular vesicles (EVs) from human 
      adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on 
      RANKL-induced osteoclast differentiation. Purified EVs were collected from the 
      supernatant of hMSCs by tangential flow filtration. Characterization of EVs 
      included typical evaluation of the size and concentration of EVs by nanoparticle 
      tracking analysis and morphology analysis using transmission electron microscopy. 
      hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived 
      macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring 
      formation and bone resorption were also reduced by EV treatment of osteoclasts. 
      In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and 
      expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To 
      elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast 
      differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that 
      has-miR122-5p was present at significantly high read counts. Overexpression of 
      miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast 
      differentiation and induced defects in F-actin ring formation and bone 
      resorption. Our results also revealed that RANKL-induced phosphorylation of p38 
      and JNK and osteoclast-specific gene expression was decreased by miR122-5p 
      transfection, which was consistent with the results of hMSC-EVs. These findings 
      suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast 
      differentiation via the downregulation of molecular mechanisms and could be a 
      preventive candidate for destructive bone diseases.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Choi, Joo-Hee
AU  - Choi JH
AD  - Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 
      41061, Republic of Korea.
FAU - Sung, Soo-Eun
AU  - Sung SE
AD  - Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 
      41061, Republic of Korea.
FAU - Kang, Kyung-Ku
AU  - Kang KK
AD  - Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 
      41061, Republic of Korea.
FAU - Lee, Sijoon
AU  - Lee S
AD  - Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 
      41061, Republic of Korea.
FAU - Sung, Minkyoung
AU  - Sung M
AD  - Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 
      41061, Republic of Korea.
FAU - Park, Wook-Tae
AU  - Park WT
AD  - Department of Orthopedic Surgery, Yeungnam University College of Medicine, 
      Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu, 42415, 
      Republic of Korea.
FAU - Kim, Young In
AU  - Kim YI
AD  - Cellexobio, Co., Ltd., Daegu, 42415, Korea.
FAU - Seo, Min-Soo
AU  - Seo MS
AD  - Department of Veterinary Tissue Engineering, Laboratory of Veterinary Tissue 
      Engineering, College of Veterinary Medicine, Kyungpook National University, 80 
      Daehak-ro, Buk-gu, Daegu, 41566, Republic of Korea. msseo@knu.ac.kr.
FAU - Lee, Gun Woo
AU  - Lee GW
AD  - Department of Orthopedic Surgery, Yeungnam University College of Medicine, 
      Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu, 42415, 
      Republic of Korea. gwlee1871@gmail.com.
LA  - eng
GR  - 2020R1F1A1072045/National Research Foundation of Korea/
GR  - 2022R1C1C1005410/National Research Foundation of Korea/
GR  - RS-2023-00219725/Regional Leading Research Center of Korea/
PT  - Journal Article
DEP - 20231129
PL  - United States
TA  - Biochem Genet
JT  - Biochemical genetics
JID - 0126611
SB  - IM
OTO - NOTNLM
OT  - Extracellular vesicles
OT  - Mesenchymal stem cells
OT  - Osteoclast
OT  - miR122-5p
EDAT- 2023/11/29 00:42
MHDA- 2023/11/29 00:42
CRDT- 2023/11/28 23:51
PHST- 2023/05/02 00:00 [received]
PHST- 2023/10/26 00:00 [accepted]
PHST- 2023/11/29 00:42 [medline]
PHST- 2023/11/29 00:42 [pubmed]
PHST- 2023/11/28 23:51 [entrez]
AID - 10.1007/s10528-023-10569-5 [pii]
AID - 10.1007/s10528-023-10569-5 [doi]
PST - aheadofprint
SO  - Biochem Genet. 2023 Nov 29. doi: 10.1007/s10528-023-10569-5.