Serum-derived extracellular vesicles inhibit osteoclastogenesis in active-phase patients with SAPHO syndrome.
Serum-derived extracellular vesicles inhibit osteoclastogenesis in active-phase patients with SAPHO syndrome.
复制标题
血清来源的细胞外囊泡抑制 SAPHO 综合征活动期患者的破骨细胞生成
DOI：
10.1177/1759720x211006966
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发表时间：
2021
影响因子：
4.2
通讯作者：
Ge W
中科院分区：
文献类型：
--
作者：
Gao Y;Chen Y;Wang L;Li C;Ge W
目的：滑膜炎、痤疮、脓疱病、骨质增生和骨炎（SAPHO）综合征是一种罕见的慢性炎症性疾病，其发病机制尚不清楚。在这项研究中，88例SAPHO患者和118名健康对照者被招募来研究血清来源的细胞外囊泡（SEV）在SAPHO综合征中的作用。研究方法：应用定量蛋白质组学技术对SEV蛋白质组进行鉴定，并采用ELISA和Western blotting技术对质谱数据进行验证。体外破骨细胞生成和成骨实验证实SEV对骨代谢的影响。结果：SAPHO SEV的串联质量标记定量蛋白质组学分析显示了参与骨代谢的差异表达蛋白。其中，血清淀粉样蛋白A-1（SAA 1）和C-反应蛋白（CRP）上调。SAPHO患者中较高的SAA 1水平通过ELISA证实。此外，SAA 1水平与CRP呈正相关，CRP是与患者病情相关的炎症标志物。体外细胞学研究证实，SAPHO SEV主要在疾病的活动期抑制患者的破骨细胞生成。进一步的分析表明，核仁素在SAPHO SEVs刺激下在活动期患者的破骨细胞中上调。结论：在这项研究中，我们确定SAA 1作为一种额外的炎症标志物，可以潜在地帮助诊断SAPHO综合征，并推测核仁素是活跃期患者破骨细胞生成的关键调节因子。
Objective: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome. Methods: Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. In vitro osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism. Results: Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. In vitro celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation. Conclusion: In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.