The Expressions of Dickkopf-Related Protein 1 and Frizzled-Related Protein Are Negatively Correlated to Local Inflammation and Osteoarthritis Severity

Xiaobin Huang, Leilei Zhong, Eefje van Helvoort, Floris Lafeber, Simon Mastbergen, Jan Hendriks, Janine N. Post, Marcel Karperien

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: 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. Design: In a cross-sectional study, SF and serum were collected from OA patients (n = 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). Results: 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. Conclusions: 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.

Original languageEnglish
JournalCartilage
DOIs
Publication statusE-pub ahead of print/First online - 4 Apr 2019

Fingerprint

Synovial Fluid
Osteoarthritis
Inflammation
Proteins
Fluids
Synovial Membrane
Celecoxib
Nitric oxide
Serum
Nitric Oxide
Cartilage
Dinoprostone
Surgery
frizzled related protein-1
Naproxen
Knee Osteoarthritis
Biomarkers
Therapeutics
Ambulatory Surgical Procedures
Immunoassay

Keywords

  • UT-Hybrid-D
  • ELISA
  • Frizzled-related protein (FRZB)
  • Gremlin 1 (GREM1)
  • osteoarthritis (OA)
  • pro-inflammatory cytokines
  • synovial fluid
  • Dickkopf-related protein 1 (DKK1)

Cite this

@article{a8561a3998ce42c3a6a20b2382e21c37,
title = "The Expressions of Dickkopf-Related Protein 1 and Frizzled-Related Protein Are Negatively Correlated to Local Inflammation and Osteoarthritis Severity",
abstract = "Objective: 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. Design: In a cross-sectional study, SF and serum were collected from OA patients (n = 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). Results: 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. Conclusions: 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.",
keywords = "UT-Hybrid-D, ELISA, Frizzled-related protein (FRZB), Gremlin 1 (GREM1), osteoarthritis (OA), pro-inflammatory cytokines, synovial fluid, Dickkopf-related protein 1 (DKK1)",
author = "Xiaobin Huang and Leilei Zhong and {van Helvoort}, Eefje and Floris Lafeber and Simon Mastbergen and Jan Hendriks and Post, {Janine N.} and Marcel Karperien",
note = "Sage deal",
year = "2019",
month = "4",
day = "4",
doi = "10.1177/1947603519841676",
language = "English",
journal = "Cartilage",
issn = "1947-6035",
publisher = "SAGE Publications",

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The Expressions of Dickkopf-Related Protein 1 and Frizzled-Related Protein Are Negatively Correlated to Local Inflammation and Osteoarthritis Severity. / Huang, Xiaobin; Zhong, Leilei; van Helvoort, Eefje; Lafeber, Floris; Mastbergen, Simon; Hendriks, Jan; Post, Janine N.; Karperien, Marcel.

In: Cartilage, 04.04.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The Expressions of Dickkopf-Related Protein 1 and Frizzled-Related Protein Are Negatively Correlated to Local Inflammation and Osteoarthritis Severity

AU - Huang, Xiaobin

AU - Zhong, Leilei

AU - van Helvoort, Eefje

AU - Lafeber, Floris

AU - Mastbergen, Simon

AU - Hendriks, Jan

AU - Post, Janine N.

AU - Karperien, Marcel

N1 - Sage deal

PY - 2019/4/4

Y1 - 2019/4/4

N2 - Objective: 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. Design: In a cross-sectional study, SF and serum were collected from OA patients (n = 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). Results: 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. Conclusions: 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.

AB - Objective: 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. Design: In a cross-sectional study, SF and serum were collected from OA patients (n = 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). Results: 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. Conclusions: 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.

KW - UT-Hybrid-D

KW - ELISA

KW - Frizzled-related protein (FRZB)

KW - Gremlin 1 (GREM1)

KW - osteoarthritis (OA)

KW - pro-inflammatory cytokines

KW - synovial fluid

KW - Dickkopf-related protein 1 (DKK1)

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U2 - 10.1177/1947603519841676

DO - 10.1177/1947603519841676

M3 - Article

JO - Cartilage

JF - Cartilage

SN - 1947-6035

ER -