Your browser doesn't support javascript.
loading
Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.
Wang, Zhen-Xing; Lin, Xiao; Cao, Jia; Liu, Yi-Wei; Luo, Zhong-Wei; Rao, Shan-Shan; Wang, Qiang; Wang, Yi-Yi; Chen, Chun-Yuan; Zhu, Guo-Qiang; Li, Fu-Xing-Zi; Tan, Yi-Juan; Hu, Yin; Yin, Hao; Li, You-You; He, Ze-Hui; Liu, Zheng-Zhao; Yuan, Ling-Qing; Zhou, Yong; Wang, Zheng-Guang; Xie, Hui.
Affiliation
  • Wang ZX; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Lin X; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Cao J; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, 410008, Hunan, China.
  • Liu YW; The Second Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Luo ZW; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Rao SS; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Wang Q; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, 410008, Hunan, China.
  • Wang YY; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Chen CY; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Zhu GQ; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Li FX; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Tan YJ; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Hu Y; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Yin H; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, 410008, Hunan, China.
  • Li YY; Department of Laboratory Medicine, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, Zhejiang, China.
  • He ZH; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Liu ZZ; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Yuan LQ; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Zhou Y; Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
  • Wang ZG; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, 410008, Hunan, China.
  • Xie H; Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
J Nanobiotechnology ; 22(1): 208, 2024 Apr 25.
Article in En | MEDLINE | ID: mdl-38664789
ABSTRACT

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.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteocytes / Osteogenesis / Tropomyosin / Mesenchymal Stem Cells / Extracellular Vesicles Limits: Animals Language: En Journal: J Nanobiotechnology Year: 2024 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteocytes / Osteogenesis / Tropomyosin / Mesenchymal Stem Cells / Extracellular Vesicles Limits: Animals Language: En Journal: J Nanobiotechnology Year: 2024 Type: Article Affiliation country: China