Maharavi Bawatharani, Mahendra Jaideep, Ponnaiyan Deepa, Rajaram Vijayalakshmi, Gyanchand Pragya, Rughwani Roshan R, Thakare Kaustubh Suresh, Kumar Gayathri, Patil Gauri
Department of Periodontics, Meenakshi Ammal Dental College and Hospital, Chennai, India.
Department of Periodontics, SRM Dental College, Ramapuram, Chennai, India.
Front Dent Med. 2025 Jul 21;6:1593218. doi: 10.3389/fdmed.2025.1593218. eCollection 2025.
BACKGROUND: Dickkopf-1 is a glycoprotein that inhibits Wingless-related integration site signaling, impairing osteoblast and osteoclast functions, leading to bone loss and systemic inflammation linked to periodontitis and rheumatoid arthritis. exacerbates rheumatoid arthritis through citrullination and inflammation, highlighting their bidirectional relationship. To date no meta-analysis has examined the role of Dickkopf-1 in periodontitis, rheumatoid arthritis, and their comorbidity. Therefore, we conducted this meta-analysis to investigate the association and role of Dickkopf-1 in these comorbid conditions. METHODS: The present study was conducted in accordance with the guidelines of Transparent Reporting of Systematic Reviews and Meta-Analyses PRISMA statement (registered at PROSPERO under the number CRD42025643227). A total of 15 studies (14 case-control and 1 cross-sectional) were selected out of 386 using databases like PubMed and Google Scholar (by BM, JM, and DP). A random-effects model evaluated Dickkopf-1 levels in serum/gingival crevicular fluid in periodontitis and rheumatoid arthritis via standardized mean difference (SMD) and 95% confidence intervals (CI). Heterogeneity and publication bias were assessed using statistical metrics, forest plots, funnel plots, Begg's test, and Egger's regression. RESULTS: A total of 386 studies were retrieved and 15 were included in the meta-analysis, encompassing 4,438 participants (2,190 cases and 2,248 controls). The pooled SMD of 2.694 ( = 0.02; 95% CI: 1.170-6.203) indicated a significant association of Dickkopf-1 with periodontitis and/or rheumatoid arthritis compared to healthy controls. However, Egger's test revealed a t-value of 3.05 ( = 0.009), indicating significant publication bias. CONCLUSION: Elevated Dickkopf-1 levels in rheumatoid arthritis and periodontitis patients suggest its critical role in the pathogenesis of both conditions. Hence, Dickkopf-1 holds therapeutic potential for managing interconnected inflammatory and bone disorders and may serve as a biomarker for diagnosing these diseases. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/search, PROSPERO CRD42025643227.
背景：Dickkopf-1是一种糖蛋白，可抑制与无翅相关整合位点信号传导，损害成骨细胞和破骨细胞功能，导致骨质流失以及与牙周炎和类风湿性关节炎相关的全身炎症。通过瓜氨酸化和炎症加剧类风湿性关节炎，突出了它们的双向关系。迄今为止，尚无荟萃分析研究Dickkopf-1在牙周炎、类风湿性关节炎及其合并症中的作用。因此，我们进行了这项荟萃分析，以研究Dickkopf-1在这些合并症中的关联和作用。 方法：本研究按照系统评价和荟萃分析的透明报告PRISMA声明指南进行（在PROSPERO注册，注册号为CRD42025643227）。使用PubMed和谷歌学术等数据库（由BM、JM和DP操作）从386项研究中筛选出15项研究（14项病例对照研究和1项横断面研究）。随机效应模型通过标准化均数差（SMD）和95%置信区间（CI）评估牙周炎和类风湿性关节炎患者血清/龈沟液中Dickkopf-1的水平。使用统计指标、森林图、漏斗图、Begg检验和Egger回归评估异质性和发表偏倚。 结果：共检索到386项研究，15项纳入荟萃分析，涵盖4438名参与者（2190例病例和2248例对照）。汇总的SMD为2.694（=0.02；95%CI：1.170 - 6.203），表明与健康对照相比，Dickkopf-1与牙周炎和/或类风湿性关节炎存在显著关联。然而，Egger检验显示t值为3.05（=0.009），表明存在显著的发表偏倚。 结论：类风湿性关节炎和牙周炎患者Dickkopf-1水平升高表明其在这两种疾病发病机制中的关键作用。因此，Dickkopf-1在管理相互关联的炎症和骨骼疾病方面具有治疗潜力，可能作为诊断这些疾病的生物标志物。 系统评价注册：https://www.crd.york.ac.uk/PROSPERO/search，PROSPERO CRD42025643227。
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