Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1
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Le résumé fourni par la source
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1
- Date Crossref
- 25/04/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Central South University Department of Orthopedics pays non établi dans la noticeUniversité ou école supérieure
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Third Xiangya Hospital pays non établi dans la noticeÉtablissement de santé
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Xiangya Hospital Central South University pays non établi dans la noticeÉtablissement de santé
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Second Xiangya Hospital of Central South University pays non établi dans la noticeÉtablissement de santé
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Zhejiang Hospital pays non établi dans la noticeÉtablissement de santé
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Second Affiliated Hospital of Zhejiang University pays non établi dans la noticeÉtablissement de santé
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Zhejiang University Department of Laboratory Medicine pays non établi dans la noticeUniversité ou école supérieure
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Hunan University pays non établi dans la noticeUniversité ou école supérieure
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National Clinical Research pays non établi dans la noticeStructure de recherche
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Hunan Key Laboratory of Angmedicine pays non établi dans la noticeStructure de recherche
Department of Orthopedics — Central South University, Third Xiangya Hospital et Xiangya Hospital Central South University, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.