Department of Orthopaedics and Spine Surgery, Ganga Hospital, 313, Mettupalayam road, Coimbatore, India.
Ganga Research Centre, No 91, Mettupalayam road, Coimbatore, 641030, India.
Eur Spine J. 2021 Sep;30(9):2586-2604. doi: 10.1007/s00586-021-06826-z. Epub 2021 Apr 9.
There is considerable controversy on the role of genetics, mechanical and environmental factors, and, recently, on subclinical infection in triggering inflammaging leading to disk degeneration. The present study investigated sequential molecular events in the host, analyzing proteome level changes that will reveal triggering factors of inflammaging and degeneration.
Ten MRI normal disks (ND) from braindead organ donors and 17 degenerated disks (DD) from surgery were subjected to in-gel-based label-free ESI-LC-MS/MS analysis. Bacterial-responsive host-defense response proteins/pathways leading to Inflammaging were identified and compared between ND and DD.
Out of the 263 well-established host-defense response proteins (HDRPs), 243 proteins were identified, and 64 abundantly expressed HDRPs were analyzed further. Among the 21 HDRPs common to both ND and DD, complement factor 3 (C3) and heparan sulfate proteoglycan 2 (HSPG2) were significantly upregulated, and lysozyme (LYZ), superoxide dismutase 3 (SOD3), phospholipase-A2 (PLA2G2A), and tissue inhibitor of metalloproteinases 3 (TIMP-3) were downregulated in DD. Forty-two specific HDRPs mainly, complement proteins, apolipoproteins, and antimicrobial proteins involved in the complement cascade, neutrophil degranulation, and oxidative-stress regulation pathways representing an ongoing host response to subclinical infection and uncontrolled inflammation were identified in DD. Protein-Protein interaction analysis revealed cross talk between most of the expressed HDRPs, adding evidence to bacterial presence and stimulation of these defense pathways.
The predominance of HDRPs involved in complement cascades, neutrophil degranulation, and oxidative-stress regulation indicated an ongoing infection mediated inflammatory process in DD. Our study has documented increasing evidence for bacteria's role in triggering the innate immune system leading to chronic inflammation and degenerative disk disease.
遗传、机械和环境因素在引发导致椎间盘退变的炎老化方面的作用存在很大争议，最近，亚临床感染在引发炎老化方面的作用也存在争议。本研究通过分析宿主的序贯分子事件，研究蛋白质组水平的变化，以揭示炎老化和退变的触发因素。
从脑死亡器官捐献者的 10 个 MRI 正常椎间盘（ND）和手术中的 17 个退变椎间盘（DD）中提取蛋白质，进行基于胶内标记的无标记 ESI-LC-MS/MS 分析。鉴定出与 ND 和 DD 相关的细菌反应宿主防御反应蛋白/途径，以确定引发炎老化的因素。
在 263 种已确立的宿主防御反应蛋白（HDRP）中，鉴定出 243 种蛋白质，进一步分析了 64 种大量表达的 HDRP。在 ND 和 DD 共有的 21 种 HDRP 中，补体因子 3（C3）和硫酸乙酰肝素蛋白聚糖 2（HSPG2）显著上调，而溶菌酶（LYZ）、超氧化物歧化酶 3（SOD3）、磷脂酶 A2（PLA2G2A）和金属蛋白酶组织抑制剂 3（TIMP-3）在 DD 中下调。在 DD 中还鉴定出 42 种主要的 HDRP，包括补体蛋白、载脂蛋白和参与补体级联、嗜中性粒细胞脱粒和氧化应激调节途径的抗菌蛋白，这些途径代表宿主对亚临床感染和失控炎症的持续反应。蛋白质-蛋白质相互作用分析显示，大多数表达的 HDRP 之间存在相互作用，这为细菌的存在及其对这些防御途径的刺激提供了证据。
参与补体级联、嗜中性粒细胞脱粒和氧化应激调节的 HDRP 占主导地位，表明 DD 中存在持续的感染介导的炎症过程。本研究提供了越来越多的证据，证明细菌在触发先天免疫系统导致慢性炎症和退行性椎间盘疾病方面的作用。
