Extracellular vesicles from human urine-derived stem cells inhibit glucocorticoid-induced osteonecrosis of the femoral head by transporting and releasing pro-angiogenic DMBT1 and anti-apoptotic TIMP1.

Animals Calcium-Binding Proteins Cell Proliferation DNA-Binding Proteins Extracellular Vesicles Femur Head Glucocorticoids Humans Osteonecrosis Rats Stem Cells Tissue Inhibitor of Metalloproteinase-1 Tumor Suppressor Proteins
Osteonecrosis of the femoral head angiogenesis apoptosis extracellular vesicles urine-derived stem cells

Journal

Acta biomaterialia
ISSN: 1878-7568
Titre abrégé: Acta Biomater
Pays: England
ID NLM: 101233144

Informations de publication

Date de publication:
15 07 2020
Historique:
received: 05 02 2020
revised: 11 05 2020
accepted: 14 05 2020
pubmed: 25 5 2020
medline: 15 5 2021
entrez: 25 5 2020
Statut: ppublish

Résumé

Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. This study aimed to determine whether EVs from human urine-derived stem cells (USC-EVs) could protect against GC-induced ONFH and focused on the impacts of USC-EVs on angiogenesis and apoptosis to explore the mechanism by which USC-EVs attenuated GC-induced ONFH. The results in vivo showed that the intravenous administration of USC-EVs at the early stage of GC exposure could rescue angiogenesis impairment, reduce apoptosis of trabecular bone and marrow cells, prevent trabecular bone destruction and improve bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reversed the GC-induced suppression of endothelial angiogenesis and activation of apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) proteins were enriched in USC-EVs and essential for the USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 attenuated the protective effects of USC-EVs against GC-induced ONFH. Our study suggests that USC-EVs are a promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1. STATEMENT OF SIGNIFICANCE: This study demonstrates that the intravenous injection of extracellular vesicles from human urine-derived stem cells (USC-EVs) at the early stage of glucocorticoid (GC) exposure efficiently protects the rats from the GC-induced osteonecrosis of the femoral head (ONFH). Moreover, this study identifies that the promotion of angiogenesis and inhibition of apoptosis by transferring pro-angiogenic DMBT1 and anti-apoptotic TIMP1 proteins contribute importantly to the USC-EVs-induced protective effects against GC-induced ONFH. This study suggests the promising prospect of USC-EVs as a new nano-sized agent for protecting against GC-induced ONFH, and the potential of DMBT1 and TIMP1 as the molecular targets for further augmenting the protective function of USC-EVs.

Identifiants

DOI: 10.1016/j.actbio.2020.05.020 PMID: 32447063
pubmed: 32447063
pii: S1742-7061(20)30290-7
doi: 10.1016/j.actbio.2020.05.020
pii:
doi:

Substances chimiques

Calcium-Binding Proteins 0
DMBT1 protein, human 0
DNA-Binding Proteins 0
Glucocorticoids 0
TIMP1 protein, human 0
Tissue Inhibitor of Metalloproteinase-1 0
Tumor Suppressor Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

208-220

Informations de copyright

Copyright © 2020. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest No conflict of interest

Auteurs

Chun-Yuan Chen (CY)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Wei Du (W)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Shan-Shan Rao (SS)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Xiangya Nursing School, Central South University, Changsha, Hunan 410013, China.

Yi-Juan Tan (YJ)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Xiong-Ke Hu (XK)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Ming-Jie Luo (MJ)

Xiangya Nursing School, Central South University, Changsha, Hunan 410013, China.

Qi-Feng Ou (QF)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Pan-Feng Wu (PF)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Li-Ming Qing (LM)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Zhe-Ming Cao (ZM)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Hao Yin (H)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Tao Yue (T)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Chao-Hong Zhan (CH)

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Jie Huang (J)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Yan Zhang (Y)

Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Yi-Wei Liu (YW)

Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Zhen-Xing Wang (ZX)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Zheng-Zhao Liu (ZZ)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Jia Cao (J)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Jiang-Hua Liu (JH)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Chun-Gu Hong (CG)

Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Ze-Hui He (ZH)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Jun-Xiao Yang (JX)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Si-Yuan Tang (SY)

Xiangya Nursing School, Central South University, Changsha, Hunan 410013, China.

Ju-Yu Tang (JY)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: tangjuyu@csu.edu.cn.

Hui Xie (H)

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan 410008, China; Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Biological Nanotechnology of National Health Commission, Changsha, Hunan 410008, China. Electronic address: huixie@csu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Extracellular vesicles from human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Protéines de liaison au calcium › Extracellular vesicles from human...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Extracellular vesicles from human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Extracellular vesicles from human...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Vésicules extracellulaires › Extracellular vesicles from human...
questionsmedicales.fr › Appareil locomoteur › Squelette › Os du membre inférieur › Fémur › Tête du fémur › Extracellular vesicles from human...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Glucocorticoïdes › Extracellular vesicles from human...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Extracellular vesicles from human...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Nécrose › Ostéonécrose › Extracellular vesicles from human...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Extracellular vesicles from human...
questionsmedicales.fr › Cellules › Cellules souches › Extracellular vesicles from human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines sécrétoires inhibitrices de protéinases › Inhibiteur tissulaire des métalloprotéinases › Inhibiteur tissulaire de métalloprotéinase-1 › Extracellular vesicles from human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Extracellular vesicles from human...