Data Sheet 1_Evaluating Dickkopf-1 as a biomarker: insights into periodontitis, rheumatoid arthritis, and their comorbidity—a systematic review and meta-analysis.pdf

BackgroundDickkopf-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. Porphyromonas gingivalis 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.
MethodsThe 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.
ResultsA 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 (p = 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 (p = 0.009), indicating significant publication bias.
ConclusionElevated 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 Registrationhttps://www.crd.york.ac.uk/PROSPERO/search, PROSPERO CRD42025643227.

背景：Dickkopf-1（Dickkopf-1）是一种可抑制Wnt信号通路（Wingless-related integration site）的糖蛋白，其可损伤成骨细胞与破骨细胞功能，进而引发骨丢失及与牙周炎、类风湿关节炎相关的全身炎症反应。牙龈卟啉单胞菌（Porphyromonas gingivalis）可通过瓜氨酸化过程与炎症反应加重类风湿关节炎，凸显了二者之间的双向关联。迄今为止，尚无荟萃分析探讨Dickkopf-1在牙周炎、类风湿关节炎及其共病中的作用。因此，本研究开展此项荟萃分析，以探究Dickkopf-1与上述共病状态的关联及其作用。

方法：本研究严格遵循《系统评价与荟萃分析优先报告条目》（PRISMA声明）开展，并已于PROSPERO平台注册（注册号：CRD42025643227）。由BM、JM与DP三名研究者通过PubMed、Google Scholar等数据库进行文献检索，从386篇初检文献中最终纳入15项研究（含14项病例对照研究与1项横断面研究）。本研究采用随机效应模型，通过标准化均数差（SMD）及95%置信区间（CI），分析牙周炎与类风湿关节炎患者血清/龈沟液中Dickkopf-1的水平。异质性与发表偏倚则通过统计指标、森林图、漏斗图、Begg检验及Egger回归进行评估。

结果：本研究共检索到386篇文献，最终纳入15项研究，共计4438名受试者（病例组2190例，对照组2248例）。合并标准化均数差为2.694（p=0.02；95%CI：1.170~6.203），提示与健康对照相比，Dickkopf-1水平与牙周炎和/或类风湿关节炎存在显著关联。然而，Egger检验显示t值为3.05（p=0.009），表明存在显著的发表偏倚。

结论：类风湿关节炎与牙周炎患者体内Dickkopf-1水平升高，提示其在两种疾病的发病机制中均发挥关键作用。因此，Dickkopf-1有望成为治疗这类相互关联的炎症与骨代谢疾病的潜在靶点，同时亦可作为上述疾病的诊断生物标志物。

系统评价注册信息：https://www.crd.york.ac.uk/PROSPERO/search，PROSPERO CRD42025643227。