不同阶段牙髓炎中牙髓血清的蛋白质组学分析

doi:10.19439/j.sjos.2025.04.002

摘要/Abstract

摘要： 目的：研究不同阶段牙髓炎中牙髓血清的蛋白质表达差异。方法：收集9例牙髓炎患者的牙髓血清,分为早期（initial pulpitis,IP）、轻中度（mild to moderate pulpitis,MP）和重度牙髓炎（severe pulpitis,SP）三组。通过蛋白质组学技术筛选差异蛋白。使用Metascape数据库进行功能注释和富集分析,并用STRING数据库分析差异蛋白的相互作用。结果：与IP组相比,MP组有20个蛋白上调,23个蛋白下调;SP组有1个蛋白上调, 44个蛋白下调。与MP组相比,SP组有9个蛋白上调和15个蛋白下调。差异蛋白主要涉及细胞对压力的响应、适应性免疫应答和Parkin-泛素蛋白酶体系统等关键生物过程。蛋白质相互作用网络分析发现CCT6A等多个关键功能节点。结论：本研究通过蛋白质组学分析了早期、轻中度与重度牙髓炎之间牙髓血清蛋白质的表达差异,可为牙髓炎的精准诊断和临床决策提供理论依据。

关键词: 牙髓炎, 牙髓血清, 蛋白质组学, 生物标志物

Abstract: PURPOSE: To investigate the differentially expressed proteins in dental pulp serum of pulpitis at different stages. METHODS: Dental pulp serum was collected from 9 pulpitis patients and categorized into three groups: initial pulpitis (IP), mild to moderate pulpitis (MP) and severe pulpitis (SP). Proteomics technology was utilized to screen for differentially expressed proteins. Functional annotation and enrichment analysis were then conducted using the Metascape database, while protein-protein interaction analysis was performed with the STRING database. RESULTS: Compared with the IP group, the MP group had 20 upregulated proteins and 23 downregulated proteins, while the SP group had one upregulated protein and 44 downregulated proteins. Compared to the MP group, the SP group had 9 upregulated proteins and 15 downregulated proteins. The differential proteins were mainly involved in key biological processes such as cellular response to stress, adaptive immune response, and the Parkin-ubiquitin proteasomal system. Protein-protein interaction network analysis identified several key functional nodes, including CCT6A. CONCLUSIONS: This study analyzed the differential expression of proteins in dental pulp serum between early, mild to moderate, and severe pulpitis, providing a theoretical basis for accurate diagnosis and clinical decision-making of pulpitis.

Key words: Pulpitis, Dental pulp serum, Proteomics, Biomarkers

中图分类号:

R781.3

隋昕, 徐华兴, 李佳洋, 秦志明, 马智菲, 周荣睿, 周强强, 韦晓玲. 不同阶段牙髓炎中牙髓血清的蛋白质组学分析[J]. 上海口腔医学, 2025, 34(4): 346-353.

Sui Xin, Xu Huaxing, Li Jiayang, Qin Zhiming, Ma Zhifei, Zhou Rongrui, Zhou Qiangqiang, Wei Xiaoling. Proteomic analysis of dental pulp serum in pulpitis at different stages[J]. Shanghai Journal of Stomatology, 2025, 34(4): 346-353.

参考文献

[1] Duncan HF, Galler KM, Tomson PL, et al.European Society of Endodontology position statement: management of deep caries and the exposed pulp[J]. Int Endod J, 2019, 52(7): 923-934.
[2] Careddu R, Duncan HF.A prospective clinical study investigating the effectiveness of partial pulpotomy after relating preoperative symptoms to a new and established classification of pulpitis[J]. Int Endod J, 2021, 54(12): 2156-2172.
[3] Ricucci D, Loghin S, Siqueira JF Jr.Correlation between clinical and histologic pulp diagnoses[J]. J Endod, 2014, 40(12): 1932-1939.
[4] Mejare IA, Axelsson S, Davidson T, et al.Diagnosis of the condition of the dental pulp: a systematic review[J]. Int Endod J, 2012, 45(7): 597-613.
[5] Zhu H, Bilgin M, Snyder M.Proteomics[J]. Annu Rev Biochem, 2003, 72: 783-812.
[6] Eckhardt A, Jágr M, Pataridis S, et al.Proteomic analysis of human tooth pulp: proteomics of human tooth[J]. J Endod, 2014, 40(12): 1961-1966.
[7] Yue W, Kim S, Jung HS, et al.Differential protein expression in human dental pulp: comparison of healthy, inflamed, and traumatic pulp[J]. J Clin Med, 2019, 8(8): 1234.
[8] Loureiro C, Buzalaf MAR, Pessan JP, et al.Comparative analysis of the proteomic profile of the dental pulp in different conditions. a pilot study[J]. Braz Dent J, 2020, 31(3): 319-336.
[9] Silva PAO, Lima SMF, Freire MS, et al.Proteomic analysis of human dental pulp in different clinical diagnosis[J]. Clin Oral Investig, 2021, 25(5): 3285-3295.
[10] Donnermeyer D, Dammaschke T, Lipski M, et al.Effectiveness of diagnosing pulpitis: a systematic review[J]. Int Endod J, 2023, 56(Suppl 3): 296-325.
[11] Wolters WJ, Duncan HF, Tomson PL, et al.Minimally invasive endodontics: a new diagnostic system for assessing pulpitis and subsequent treatment needs[J]. Int Endod J, 2017, 50(9): 825-829.
[12] Mente J, Petrovic J, Gehrig H, et al.A prospective clinical pilot study on the level of matrix metalloproteinase-9 in dental pulpal blood as a marker for the state of inflammation in the pulp tissue[J]. J Endod, 2016, 42(2): 190-197.
[13] Cushley S, Duncan HF, Lappin MJ, et al.Pulpotomy for mature carious teeth with symptoms of irreversible pulpitis: a systematic review[J]. J Dent, 2019, 88: 103158.
[14] Taha NA, Ahmad MB, Ghanim A.Assessment of mineral trioxide aggregate pulpotomy in mature permanent teeth with carious exposures[J]. Int Endod J, 2017, 50(2): 117-125.
[15] Rechenberg DK, Zehnder M.Call for a review of diagnostic nomenclature and terminology used in endodontics[J]. Int Endod J, 2020, 53(10): 1315-1317.
[16] Cooper PR, Takahashi Y, Graham LW, et al.Inflammation-regeneration interplay in the dentine-pulp complex[J]. J Dent, 2010, 38(9): 687-697.
[17] Khorasani MMY, Hassanshahi G, Brodzikowska A, et al.Role(s) of cytokines in pulpitis: latest evidence and therapeutic approaches[J]. Cytokine, 2020, 126: 154896.
[18] Zehnder M, Belibasakis GN.A critical analysis of research methods to study clinical molecular biomarkers in endodontic research[J]. Int Endod J, 2022, 55(Suppl 1): 37-45.
[19] Sharma R, Kumar V, Logani A, et al.Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible pulpitis-a preliminary study[J]. Int Endod J, 2021, 54(4): 479-489.
[20] Brizuela C, Meza G, Mercadé M, et al.Inflammatory biomarkers in dentinal fluid as an approach to molecular diagnostics in pulpitis[J]. Int Endod J, 2020, 53(9): 1181-1191.
[21] Ozok AR, Wu MK, Ten Cate JM, et al.Effect of dentinal fluid composition on dentin demineralization in vitro[J]. J Dent Res, 2004, 83(11): 849-853.
[22] Rechenberg D, Zehnder M.Molecular diagnostics in endodontics[J]. Endod Topics, 2014, 30(1): 51-65.
[23] Elsalhy M, Azizieh F, Raghupathy R.Cytokines as diagnostic markers of pulpal inflammation[J]. Int Endod J, 2013, 46(6): 573-580.
[24] Zeng G, Wang J, Huang Y, et al.Overexpressing CCT6A contributes to cancer cell growth by affecting the G1-To-S phase transition and predicts a negative prognosis in hepatocellular carcinoma[J]. Onco Targets Ther, 2019, 12: 10427-10439.
[25] Grantham J, Brackley KI, Willison KR.Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells[J]. Exp Cell Res, 2006, 312(12): 2309-2324.
[26] Zhou X, Zhang B, Zheng G, et al.Novel necroptosis-related gene signature for predicting early diagnosis and prognosis and immunotherapy of gastric cancer[J]. Cancers(Basel), 2022, 14(16):3891.
[27] Macario AJL, Conway de Macario E. Chaperonins in cancer: expression, function, and migration in extracellular vesicles[J]. Semin Cancer Biol, 2022, 86(Pt 1): 26-35.
[28] Zheng Z, Li Y, Lu X, et al.A novel mTOR-associated gene signature for predicting prognosis and evaluating tumor immune microenvironment in lung adenocarcinoma[J]. Comput Biol Med, 2022, 145: 105394.
[29] Ying Z, Tian H, Li Y, et al.CCT6A suppresses SMAD2 and promotes prometastatic TGF-beta signaling[J]. J Clin Invest, 2017, 127(5): 1725-1740.
[30] Chen Y, Chen Y, Liu W.Chaperonin containing TCP1 subunit 6A may activate Notch and Wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma[J]. Cancer Biol Ther, 2024, 25(1): 2287122.
[31] Xia X, Zhao S, Chen W, et al.CCT6A promotes esophageal squamous cell carcinoma cell proliferation, invasion and epithelial-mesenchymal transition by activating TGF-beta/Smad/c-Myc pathway[J]. Ir J Med Sci, 2023, 192(6): 2653-2660.
[32] Behrens P, Brinkmann U, Wellmann A.CSE1L/CAS: its role in proliferation and apoptosis[J]. Apoptosis, 2003, 8(1): 39-44.
[33] Li G, Li R, Wang W, et al.DDX27 regulates oral squamous cell carcinoma development through targeting CSE1L[J]. Life Sci, 2024, 340: 122479.
[34] Tai CJ, Hsu CH, Shen SC, et al.Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis[J]. J Exp Clin Cancer Res, 2010, 29(1): 110.
[35] Tanaka T, Ohkubo S, Tatsuno I, et al.hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes[J]. Cell, 2007, 130(4): 638-650.
[36] Cang Y, Zhang J, Nicholas S A, et al.DDB1 is essential for genomic stability in developing epidermis[J]. Proc Natl Acad Sci USA, 2007, 104(8): 2733-2737.
[37] Falini B, Brunetti L, Sportoletti P, et al.NPM1-mutated acute myeloid leukemia: from bench to bedside[J]. Blood, 2020, 136(15): 1707-1721.
[38] Miao Q, Xu Y, Yin H, et al.KRT8 phosphorylation regulates the epithelial-mesenchymal transition in retinal pigment epithelial cells through autophagy modulation[J]. J Cell Mol Med, 2020, 24(5): 3217-3228.
[39] Gomez HL, Felipe-Medina N, Condezo YB, et al.The PSMA8 subunit of the spermatoproteasome is essential for proper meiotic exit and mouse fertility[J]. PLoS Genet, 2019, 15(8): e1008316.
[40] Zhu X, Huang B, Zhao F, et al.p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-kappaB signaling pathway[J]. Nucleic Acids Res, 2023, 51(5): 2195-2214.
[41] Rosenzweig R, Nillegoda NB, Mayer MP, et al.The Hsp70 chaperone network[J]. Nat Rev Mol Cell Biol, 2019, 20(11): 665-680.
[42] Pohl C, Dikic I.Cellular quality control by the ubiquitin-proteasome system and autophagy[J]. Science, 2019, 366(6467): 818-22.
[43] 古丽其合热·阿布来提, 秦旭, 朱光勋. 线粒体自噬在牙周炎发生发展过程中的研究进展[J]. 国际口腔医学杂志, 2024, 51(1): 68-73.
[44] Li X, Zhao Y, Peng H, et al.Robust intervention for oxidative stress-induced injury in periodontitis via controllably released nanoparticles that regulate the ROS-PINK1-Parkin pathway[J]. Front Bioeng Biotechnol, 2022, 10: 1081977.
[45] Liu B, Zhang J, Liu G, et al.Expression of PINK1 and Parkin in human apical periodontitis[J]. Int Endod J, 2022, 55(8): 870-881.
[46] Yang CN, Kok SH, Wang HW, et al.Simvastatin alleviates bone resorption in apical periodontitis possibly by inhibition of mitophagy-related osteoblast apoptosis[J]. Int Endod J, 2019, 52(5): 676-688.
[47] Cockram PE, Kist M, Prakash S, et al.Ubiquitination in the regulation of inflammatory cell death and cancer[J]. Cell Death Differ, 2021, 28(2): 591-605.
[48] Iyengar PV.Regulation of ubiquitin enzymes in the TGF-beta pathway[J]. Int J Mol Sci, 2017, 18(4): 877-886.