Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
Department of Rheumatology & Clinical Immunology, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, University Utrecht, the Netherlands.
Cartilage. 2021 Oct;12(4):496-504. doi: 10.1177/1947603519841676. Epub 2019 Apr 4.
To investigate the presence of WNT antagonists Dickkopf-related protein 1 (DKK1), Frizzled-related protein (FRZB) and BMP antagonist Gremlin 1 (GREM1) in synovial fluid (SF) and serum, respectively, from end-stage knee osteoarthritis (OA) patients, and correlate their expression with other markers of OA.
In a cross-sectional study, SF and serum were collected from OA patients ( = 132). The concentrations of DKK1, FRZB and GREM1 in SF and serum were determined using immunoassays. Correlation measurements were performed between groups and previously assessed disease markers, such as synovium nitric oxide (NO), inerleukin-1β (IL1β), tumor necrosis factor-α (TNFα), and prostaglandin E2 (PGE2).
The OA patients with the celecoxib treatment till surgery have higher median SF FRZB values compared with the control (no treatment); the celecoxib 3-days before surgery stopped treatment group has higher median serum FRZB values than the control and the naproxen treatment group. The combinational analysis of SF DKK1 and SF FRZB negatively correlated with macroscopic cartilage scores and histological synovium scores in OA patients. The expression of DKK1 and FRZB in SF showed the same expression trend as their expression in serum. Furthermore, the SF concentration of DKK1 was positively correlated with FRZB in both SF and serum. In contrast, it was negatively correlated with synovium NO and IL1β. SF FRZB was negatively correlated with synovium NO, IL1β, cartilage PGE2, and age.
Our findings suggest DKK1 and FRZB were negatively correlated with OA severity and multiple pro-inflammatory cytokines. Our data indicate that DKK1 and FRZB can be joint disease-specific biomarkers.
分别研究骨关节炎(OA)终末期患者关节滑液(SF)和血清中 WNT 拮抗剂 Dickkopf 相关蛋白 1(DKK1)、卷曲相关蛋白(FRZB)和骨形态发生蛋白拮抗剂 Gremlin 1(GREM1)的存在,并将其表达与 OA 的其他标志物相关联。
在一项横断面研究中,收集了 OA 患者(n=132)的 SF 和血清。使用免疫测定法测定 SF 和血清中 DKK1、FRZB 和 GREM1 的浓度。在组间进行相关性测量,并与之前评估的疾病标志物(如滑膜一氧化氮(NO)、白细胞介素 1β(IL1β)、肿瘤坏死因子-α(TNFα)和前列腺素 E2(PGE2))进行关联。
与对照组(未治疗)相比,接受塞来昔布治疗直至手术的 OA 患者 SF FRZB 中位数更高;手术前 3 天停止塞来昔布治疗组的血清 FRZB 中位数高于对照组和萘普生治疗组。SF DKK1 和 SF FRZB 的联合分析与 OA 患者的宏观软骨评分和组织学滑膜评分呈负相关。SF 和血清中 DKK1 和 FRZB 的表达呈相同的表达趋势。此外,SF 中 DKK1 的浓度与 SF 和血清中 FRZB 的浓度呈正相关。相反,它与滑膜 NO 和 IL1β呈负相关。SF FRZB 与滑膜 NO、IL1β、软骨 PGE2 和年龄呈负相关。
我们的研究结果表明 DKK1 和 FRZB 与 OA 严重程度和多种促炎细胞因子呈负相关。我们的数据表明 DKK1 和 FRZB 可以作为联合疾病特异性生物标志物。