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富含血小板的血浆衍生外泌体通过促进巨噬细胞中 NLRP3 自噬降解来减轻椎间盘退变。

Platelet-rich plasma-derived exosomes attenuate intervertebral disc degeneration by promoting NLRP3 autophagic degradation in macrophages.

机构信息

Division of Spinal Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Orthopaedics, Affiliated Hengyang Hospital, Southern Medical University (Hengyang Central Hospital), Hengyang, China.

Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China.

出版信息

Int Immunopharmacol. 2022 Sep;110:108962. doi: 10.1016/j.intimp.2022.108962. Epub 2022 Jun 24.

DOI:10.1016/j.intimp.2022.108962
PMID:35753124
Abstract

Intervertebral disc degeneration (IDD) is a common orthopedic multifactorial disease associated with spine-related disorders, such as low back pain. Recent studies have shown that both platelet-rich plasma (PRP) and exosomes could be used to treat IDD, but the effects and mechanism of PRP-derived exosomes in the treatment of IDD are still unclear. This study showed that PRP-derived exosomes inhibited the polarization of M1 macrophages by regulating the NF-κB and MAPK pathways and affected the polarization of M2 macrophages by regulating STAT6 phosphorylation. Additionally, PRP-derived exosomes promoted the autophagic degradation of NLRP3 by increasing NLRP3 ubiquitination and reducing IL-1β and Caspase-1 production. Moreover, PRP-derived exosomes could reduce IL-1β-induced apoptosis of nucleus pulposus cells. Lastly, in vivo experiments confirmed that PRP-derived exosomes reduced the expression of inflammatory mediators and apoptotic factors, which could thereby alleviate the progression of IDD. Taken together, these data showed that PRP-derived exosomes could alleviate the IDD-associated inflammation by regulating the ubiquitination and autophagic degradation of NLRP3 inflammasome, providing new insights into the treatment of IDD.

摘要

椎间盘退变(IDD)是一种常见的骨科多因素疾病,与脊柱相关疾病有关,如腰痛。最近的研究表明,富血小板血浆(PRP)和外泌体均可用于治疗 IDD,但 PRP 衍生的外泌体在治疗 IDD 中的作用和机制尚不清楚。本研究表明,PRP 衍生的外泌体通过调节 NF-κB 和 MAPK 通路抑制 M1 巨噬细胞的极化,并通过调节 STAT6 磷酸化影响 M2 巨噬细胞的极化。此外,PRP 衍生的外泌体通过增加 NLRP3 泛素化和减少 IL-1β 和 Caspase-1 的产生来促进 NLRP3 的自噬降解。此外,PRP 衍生的外泌体可减少 IL-1β 诱导的髓核细胞凋亡。最后,体内实验证实 PRP 衍生的外泌体可通过调节 NLRP3 炎症小体的泛素化和自噬降解来减轻 IDD 相关炎症,为 IDD 的治疗提供了新的思路。

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