Abstract

Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a “factory” to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.

Details

Title
Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG
Author
Chun-Yuan, Chen 1 ; Shan-Shan, Rao 2 ; Yi-Juan, Tan 3 ; Ming-Jie Luo 4 ; Xiong-Ke, Hu 3 ; Yin, Hao 1 ; Huang, Jie 1 ; Hu, Yin 1 ; Zhong-Wei, Luo 1 ; Zheng-Zhao, Liu 5 ; Zhen-Xing, Wang 3 ; Cao, Jia 3 ; Yi-Wei, Liu 5 ; Hong-Ming, Li 1 ; Chen, Yang 6 ; Du, Wei 7 ; Jiang-Hua, Liu 1 ; Zhang, Yan 5 ; Tuan-Hui, Chen 3 ; Hao-Ming, Liu 3 ; Wu, Ben 3 ; Yue, Tao 1 ; Yi-Yi, Wang 1 ; Xia, Kun 1 ; Peng-Fei, Lei 8 ; Si-Yuan, Tang 4 ; Xie, Hui 9 

1  Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China 
2  Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Xiangya School of Nursing, Central South University, Changsha, Hunan, China 
3  Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China 
4  Xiangya School of Nursing, Central South University, Changsha, Hunan, China 
5  Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China 
6  Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China 
7  Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, Hunan, China 
8  Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China 
9  Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan, China; Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China 
Pages
1-14
Publication year
2019
Publication date
Jun 2019
Publisher
Springer Nature B.V.
ISSN
20954700
e-ISSN
20956231
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41413-019-0056-9
ProQuest document ID
2247651916
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.