Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease

Liu, Xixi; Chen, Chunyuan; Jiang, Yaling; Wan, Meidan; Jiao, Bin; Liao, Xinxin; Rao, Shobha; Hong, Chengyu; Yang, Qingda; Zhu, Yinian; Liu, Qianqian; Luo, Zhenyue; Duan, Ran; Wang, Yiyi; Tan, Yuyong; Cao, Jia; Liu, Zhengzhao; Wang, Zhenxing; Xie, Haiyang; Shen, Lu

doi:10.7150/ijbs.79461

Cited by 16 publications

(14 citation statements)

References 58 publications

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“…Particularly, due to the protection of EVs, they are not only stable in the extracellular environment, such as blood(Chen et al, 2008), but also free to pass through the blood-brain barrier, indicating that miRNAs may work as the linkers between brain and bone. Consistently, a previous study reported that miR-483-5p, stored in brain-derived EVs, could promote bone-fat imbalance in Alzheimer’s disease(Liu et al, 2023). Take the consideration that several endogenic miRNAs in the brain(Olejniczak et al, 2018) and blood(Makrygianni & Chrousos, 2023) were reported to change their expression levels after chronic psychological stress, it’s deducible that psychological stress may interfere the bone metabolism through brain-derived miRNAs.…”

Section: Introductionsupporting

confidence: 84%

“…miR-328a-3p and miR-150-5p enriched in EVs from hippocampus after traumatic brain injury accelerate bone healing(Xia et al, 2021). miR-384-5p in brain-derived EVs induces a bone-fat imbalance and bone loss in Alzheimer’s disease (Liu et al, 2023). Psychological stress, one of the most common type of neuropsychiatric disorders, is well established as a promoter of osteoporosis, so could miRNAs act as messengers between it and bone homeostasis?…”

Section: Discussionmentioning

confidence: 99%

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Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast

Zhang,

Li,

Huang

et al. 2024

Preprint

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It has been well-validated that chronic psychological stress leads to bone loss, but the underlying mechanism remains unclarified. In this study, we established and analyzed the chronic unpredictable mild stress (CUMS) mice to investigate the miRNA-related pathogenic mechanism involved in psychological stress-induced osteoporosis. Our result found that these CUMS mice exhibited osteoporosis phenotype that mainly attributed to the abnormal activities of osteoclasts. Subsequently, miRNA sequencing and other analysis showed that miR-335-3p, which is normally highly expressed in the brain, was significantly down-regulated in the nucleus ambiguous (NAC), serum, and bone of the CUMS mice. Additionally,in vitrostudies detected that miR-335-3p is important for osteoclast differentiation, with its direct targeting site in Fos. Further studies demonstrated Fos was upregulated in CUMS osteoclast, and the inhibition of Fos suppressed the accelerated osteoclastic differentiation, as well as the expression of osteoclastic genes, such as Nfatc1, Acp5, Mmp9, in miR-335-3p restrained osteoclasts. In conclusion, this work indicated that psychological stress may down-regulate the miR-335-3p expression, which resulted in the accumulation of Fos and the up-regulation of NFACT1 signaling pathway in osteoclasts, leading to its accelerated differentiation and abnormal activity. These results decipher a previously unrecognized paradigm that miRNA can act as a link between psychological stress and bone metabolism.Impact statementmiR-335-3p, which targets FOS and inhibits its activation of NFATC1 signaling, is an important regulator for osteoclast function and responsible for the psychological stress induced osteoporosis

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Section: Introductionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast

Zhang,

Li,

Huang

et al. 2024

Preprint

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“…Insufficient osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are considered to be key factors in the pathogenesis of OP. 137 Studies have found that activation and blocking of the Notch1 signaling pathway can affect the differentiation of BMSCs. 138 HCG18 has been found to inhibit the differentiation of BMSCs by targeting the miR-30a-5p/NOTCH1 axis.…”

Section: Bone-related Diseasesmentioning

confidence: 99%

“…HCG18, as a ceRNA, can promote the progression of OP. Insufficient osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are considered to be key factors in the pathogenesis of OP 137 . Studies have found that activation and blocking of the Notch1 signaling pathway can affect the differentiation of BMSCs 138 .…”

Section: Hcg18 In Human Diseasementioning

confidence: 99%

The role of lncRNA HCG18 in human diseases

Long,

Zhou,

Zhang

et al. 2024

Cell Biochemistry & Function

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A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.

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“…These vesicles, encompassing both exosomes (30-100 nm) derived from endosomal compartments and the more heterogeneous ectosomes (50-1000 nm), encapsulate a microcosm of the cellular interior, carrying nucleic acids, proteins, lipids, and metabolites across biological frontiers [8][9][10]. Their repertoire extends beyond mere waste disposal to orchestrating physiological and pathological processes, facilitated by their capacity to breach the blood-brain barrier (BBB) and to mediate crosstalk between the CNS and peripheral tissues [7,8,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Liu,

Shen,

Wan

et al. 2024

J Nanobiotechnol

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Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies.Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: “neurodegenerative disease” OR “Alzheimer’s disease” OR “Parkinson’s disease” OR “Amyotrophic lateral sclerosis” AND “extracellular vesicles” OR “exosomes” OR “outer membrane vesicles” AND “drug delivery systems” AND “blood-brain barrier”. MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.

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Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease

Cited by 16 publications

References 58 publications

Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast

Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast

The role of lncRNA HCG18 in human diseases

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

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