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骨细胞衍生的细胞外囊泡对阿尔茨海默病的保护作用随着衰老而减弱。

The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging.

机构信息

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

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

出版信息

Adv Sci (Weinh). 2022 Jun;9(17):e2105316. doi: 10.1002/advs.202105316. Epub 2022 May 4.

DOI:10.1002/advs.202105316
PMID:35508803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9189667/
Abstract

Both Alzheimer's disease (AD) and osteoporosis (OP) are common age-associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCY -EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCY -EVs are diminished in aged osteocyte-derived EVs (OCY -EVs). Based on the self-constructed OCY-EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY-EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a-shRNA adenovirus inhibits OCY -EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCY -EVs, compared to OCY -EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY-EV as a regulator of brain health, suggesting a novel mechanism in bone-brain communication.

摘要

阿尔茨海默病 (AD) 和骨质疏松症 (OP) 都是常见的与年龄相关的退行性疾病，与临床流行病学密切相关。然而，目前对于大脑和骨骼之间缺乏明确的病理关系。本研究发现，骨中含量最丰富的成骨细胞，即年轻的成骨细胞，分泌细胞外囊泡 (OCY-EVs)，可改善 APP/PS1 小鼠和模型细胞的认知障碍和 AD 发病机制。而在衰老的成骨细胞衍生的 EVs (OCY-EVs) 中，这些 OCY-EVs 的益处减少了。基于自行构建的 OCY-EVs 示踪转基因小鼠模型和体内荧光成像系统，观察到 OCY-EVs 在生理和病理条件下被转运到大脑。在 Aβ40 诱导的年轻 AD 模型小鼠的海马给药中，Rab27a-shRNA 腺病毒抑制骨中成骨细胞来源的 OCY-EVs 分泌并加重认知障碍。蛋白质组学定量分析表明，与 OCY-EVs 相比，OCY-EVs 富含多种 AD 通路的保护因子。该研究揭示了 OCY-EV 作为大脑健康调节剂的作用，提示了骨脑通讯的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/2f556ecf201e/ADVS-9-2105316-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/5874ac9c6924/ADVS-9-2105316-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/5bcf936fe9a3/ADVS-9-2105316-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/e18b531a580c/ADVS-9-2105316-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/d22ee14ee410/ADVS-9-2105316-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/643de4c8b3df/ADVS-9-2105316-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/3e31e97a90e6/ADVS-9-2105316-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/aa9b0cb60eba/ADVS-9-2105316-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/2f556ecf201e/ADVS-9-2105316-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/5874ac9c6924/ADVS-9-2105316-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/5bcf936fe9a3/ADVS-9-2105316-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/e18b531a580c/ADVS-9-2105316-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/d22ee14ee410/ADVS-9-2105316-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/643de4c8b3df/ADVS-9-2105316-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/3e31e97a90e6/ADVS-9-2105316-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/aa9b0cb60eba/ADVS-9-2105316-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/9189667/2f556ecf201e/ADVS-9-2105316-g004.jpg

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2
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Nat Rev Dis Primers. 2021 May 13;7(1):33. doi: 10.1038/s41572-021-00269-y.
3
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Biomedicines. 2025 Jun 12;13(6):1443. doi: 10.3390/biomedicines13061443.
4
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5
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