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Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.

Publication ,  Journal Article
Hsueh, M-F; Zhang, X; Wellman, SS; Bolognesi, MP; Kraus, VB
Published in: Arthritis Rheumatol
January 2021

OBJECTIVE: To evaluate the role of immune cells and their effector cytokines in the pathogenesis and progression of knee osteoarthritis (OA) in matched OA synovial fluid (SF) and synovial tissue samples. METHODS: Cells from matched samples of synovial tissue and SF acquired from individuals undergoing total knee replacement for OA (n = 39) were characterized for immune cell-associated surface markers and intracellular cytokine expression using polychromatic flow cytometry. Additional individuals with radiographic knee OA (Kellgren/Lawrence severity grades ≥1) who had available etarfolatide (inflammatory cell) imaging (n = 26) or baseline and 3-year data on progression of radiographic knee OA (n = 85) were also assessed. SF cytokine concentrations in all cohorts were evaluated for associations with synovial tissue and SF cell phenotypes and severity of radiographic knee OA. RESULTS: Macrophages (predominant in the synovial tissue, 53% of total cells) and neutrophils (predominant in the SF, 26% of total cells) were the major immune cell populations identified in the OA knee joints, exhibiting expression of or association with transforming growth factor β1 (TGFβ1) and elastase, respectively, in the SF. Expression levels of TGFβ1 and elastase were significantly associated with severity of radiographic knee OA. Baseline SF concentrations of TGFβ1 and elastase along with radiographic knee OA severity scores were predictive of knee OA progression, with areas under the receiver operating characteristic curves of 0.810 (for TGFβ1), 0.806 (for elastase), and 0.846 (for both TGFβ1 and elastase combined), with greater stability of prediction when both markers were utilized. CONCLUSION: Our findings demonstrate the hitherto underappreciated role of neutrophils in the sterile inflammatory process and progression of OA. Two soluble mediators, SF elastase and TGFβ1, are strong predictors of knee OA progression, reflecting a synergistic role of neutrophil and macrophage populations in the pathogenesis and worsening of OA that could potentially be utilized to identify patients who may have a greater risk of more rapid disease progression.

Duke Scholars

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Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

January 2021

Volume

73

Issue

1

Start / End Page

89 / 99

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • T-Lymphocytes
  • Synovial Membrane
  • Synovial Fluid
  • Osteoarthritis, Knee
  • Osteoarthritis
  • Neutrophils
  • Middle Aged
  • Male
  • Macrophages
 

Citation

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Chicago
ICMJE
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Hsueh, M.-F., Zhang, X., Wellman, S. S., Bolognesi, M. P., & Kraus, V. B. (2021). Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression. Arthritis Rheumatol, 73(1), 89–99. https://doi.org/10.1002/art.41486
Hsueh, Ming-Feng, Xin Zhang, Samuel S. Wellman, Michael P. Bolognesi, and Virginia B. Kraus. “Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.Arthritis Rheumatol 73, no. 1 (January 2021): 89–99. https://doi.org/10.1002/art.41486.
Hsueh M-F, Zhang X, Wellman SS, Bolognesi MP, Kraus VB. Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression. Arthritis Rheumatol. 2021 Jan;73(1):89–99.
Hsueh, Ming-Feng, et al. “Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.Arthritis Rheumatol, vol. 73, no. 1, Jan. 2021, pp. 89–99. Pubmed, doi:10.1002/art.41486.
Hsueh M-F, Zhang X, Wellman SS, Bolognesi MP, Kraus VB. Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression. Arthritis Rheumatol. 2021 Jan;73(1):89–99.
Journal cover image

Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

January 2021

Volume

73

Issue

1

Start / End Page

89 / 99

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • T-Lymphocytes
  • Synovial Membrane
  • Synovial Fluid
  • Osteoarthritis, Knee
  • Osteoarthritis
  • Neutrophils
  • Middle Aged
  • Male
  • Macrophages