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神经源性异位骨化中的器官间通讯：脑源性细胞外囊泡的作用。

Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles.

机构信息

Department of Stomatology, Tangdu Hospital & State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.

State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.

出版信息

Bone Res. 2024 Feb 22;12(1):11. doi: 10.1038/s41413-023-00310-8.

DOI:10.1038/s41413-023-00310-8
PMID:38383487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10881583/
Abstract

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction, such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury. Brain-derived extracellular vesicles (BEVs) are released after traumatic brain injury. These BEVs contain pathogens and participate in interorgan communication to initiate secondary injury in distal tissues. After achillotenotomy, the phagocytosis of BEVs by fibroblasts induces pyroptosis, which is a highly inflammatory form of lytic programmed cell death, in the injured tendon. Fibroblast pyroptosis leads to an increase in calcium and phosphorus concentrations and creates a microenvironment that promotes osteogenesis. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk suppressed fibroblast pyroptosis and effectively prevented the onset of heterotopic ossification after neuronal injury. The use of a pyroptosis inhibitor represents a potential strategy for the treatment of neurogenic heterotopic ossification.

摘要

脑源性细胞外囊泡通过运输病原体参与创伤性脑损伤后的器官间通讯，从而引发继发性损伤。脑源性细胞外囊泡中包裹的炎性小体相关蛋白可以穿过血脑屏障到达远端组织。这些蛋白引发炎症功能障碍，例如神经性异位骨化。这种复发性疾病对患者的影响非常严重，因为其发病机制相对未知，且缺乏有效的预防干预策略。因此，建立了一种由创伤性脑损伤和跟腱切断术联合诱导的神经性异位骨化大鼠模型来解决这两个问题。损伤肌腱的组织学检查显示异位钙化和成纤维细胞焦亡共存。进一步在体外和体内研究了脑源性细胞外囊泡、成纤维细胞焦亡和异位钙化之间的关系。静脉注射焦亡抑制剂 Ac-YVAD-cmk 逆转了体内神经性异位骨化的发展。本研究强调了脑源性细胞外囊泡在神经性异位骨化发病机制中的作用，并为创伤性脑损伤后预防神经性异位骨化提供了一种潜在策略。脑源性细胞外囊泡（BEVs）在创伤性脑损伤后释放。这些 BEVs 包含病原体，并参与器官间通讯，以在远端组织中引发继发性损伤。跟腱切断术后，BEVs 被成纤维细胞吞噬，导致损伤肌腱中的成纤维细胞发生焦亡，这是一种高度炎症性的溶细胞程序性细胞死亡形式。成纤维细胞焦亡导致钙和磷浓度增加，并产生促进成骨的微环境。静脉注射焦亡抑制剂 Ac-YVAD-cmk 抑制了成纤维细胞焦亡，并有效预防了神经元损伤后异位骨化的发生。使用焦亡抑制剂代表了治疗神经性异位骨化的一种潜在策略。

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Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles.

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引用本文的文献

[1]
Bidirectional Interaction Between the Brain and Bone in Traumatic Brain Injury.

Adv Sci (Weinh). 2025-8

[2]
Risk factors for the development of heterotopic ossification of the elbow in children with untreated chronic Monteggia fractures: a radiographic review of 274 cases.

J Orthop Traumatol. 2025-4-26

[3]
Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.

Int J Biol Sci. 2025-1-1

[4]
Engineered melatonin-pretreated plasma exosomes repair traumatic spinal cord injury by regulating miR-138-5p/SOX4 axis mediated microglia polarization.

J Orthop Translat. 2024-10-24

[5]
Recent progress of methods for cuproptosis detection.

Front Mol Biosci. 2024-9-4

[6]
Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond.

Int J Mol Sci. 2024-3-20

本文引用的文献

[1]
Intercellular mitochondrial component transfer triggers ischemic cardiac fibrosis.

Sci Bull (Beijing). 2023-8-30

[2]
Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-β/Smad signaling in a growing mouse model of osteogenesis imperfecta.

J Orthop Translat. 2022-11-15

[3]
Vascular Calcification: In Vitro Models under the Magnifying Glass.

Biomedicines. 2022-10-6

[4]
The Functions and Mechanisms of Basic Fibroblast Growth Factor in Tendon Repair.

Front Physiol. 2022-6-13

[5]
Extracellular vesicles from lung tissue drive bone marrow neutrophil recruitment in inflammation.

J Extracell Vesicles. 2022-5

[6]
Sustained local ionic homeostatic imbalance caused by calcification modulates inflammation to trigger heterotopic ossification.

Acta Biomater. 2022-6

[7]
A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.

Cell Stem Cell. 2022-4-7

[8]
Interleukin-1 Is Overexpressed in Injured Muscles Following Spinal Cord Injury and Promotes Neurogenic Heterotopic Ossification.

J Bone Miner Res. 2022-3

[9]
LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome.

Cell Death Discov. 2021-11-6

[10]
Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide.

Adv Sci (Weinh). 2022-1

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