Cited by 68Osteoarthritis Treatment and MechanismsChemokine receptors and signalingRheumatoid Arthritis Research and Therapies

CCL3/CCR1 mediates CD14+CD16− circulating monocyte recruitment in knee osteoarthritis progression

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Zhao, X., Gu, M., Xu, X., Wen, X., Yang, G., Li, L., Sheng, P., Meng, F.·2020·Osteoarthritis and Cartilage

Abstract

Objectives Monocyte-derived macrophages, as the predominant immune cell type that is increased in inflamed synovium, play a vital role during knee osteoarthritis (KOA) progression. However, the mechanisms underlying the recruitment of circulating monocytes to osteoarthritic knees remain uncertain. Based on previous data obtained from plasma, we investigated the contributions of CCL2, CCL3, CCL4 and their cognate receptors in circulating monocyte chemotaxis and KOA development. Methods Using flow cytometry staining, we characterized the expression patterns of the chemokine receptors in CD14+CD16- circulating monocytes from KOA patients and healthy volunteers. The expression of chemokines in synovial fluids, synovium and cartilage was investigated in KOA patients and in patients without KOA. The role of chemokines and their cognate receptors in the chemotaxis of CD14+CD16- circulating monocytes was assessed using chemokine neutralizing antibodies (NA) and receptor antagonists in vitro and in vivo. Results The majority of CD14+CD16- circulating monocytes were CCR1-and CCR2-positive. CCL2, CCL3 and CCL4 were elevated in synovial fluid of KOA patients compared with that of controls. The most likely source of these chemokines is inflamed synovium and cartilage in the osteoarthritic knee. The CCL3/CCR1 and CCL2/CCR2 axes showed substantial ability to recruit CD14+CD16- monocytes in transwell assays. Similar results were confirmed in a mouse model of collagenase-induced KOA (CIA) in which blocking either the CCL3/CCR1 axis or the CCL2/CCR2 axis reduced synovial hyperplasia and F4/80+ macrophage infiltration. Conclusions Our findings suggested that, analogous to the CCL2/CCR2 axis, CCL3 produced in osteoarthritic knees can chemoattract circulating monocytes to the inflamed synovium through CCR1.

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  1. Katschke Jr KJ, Rottman JB, Ruth JH, Qin S, Wu L, LaRosa G, et al. Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macro- phages in rheumatoid arthritis. Arthritis Rheum: Off J Am Coll Rheumatol 2001;44(5):1022e32.

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Authors
Zhao, X., Gu, M., Xu, X., Wen, X., Yang, G., Li, L., Sheng, P., & Meng, F.
Affiliations
  • The First Affiliated Hospital, Sun Yat-sen University (CN)
  • Moffitt Cancer Center (US)
Corresponding author
  • Zhao, X.
  • Meng, F.
Venue
Osteoarthritis and Cartilage
Publisher
Elsevier BV
Published
2020-05
Volume
28
Issue
5
Pages
613-625
ISSN
1063-4584 (ISSN-L)
OpenAlex
W3003671378
Cited by
66
References
46
Citations by year
2026: 4 · 2025: 23 · 2024: 11 · 2023: 12 · 2022: 9 · 2021: 3 · 2020: 4
FWCI
5.47
Type
journal article
Language
en
Open access
Locations
  • Osteoarthritis and Cartilage (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Natural Science Foundation of Guangdong Province
  • National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
knee osteoarthritis, CCL2/CCR2 axis, carbon tetrachloride, monocyte recruitment, CD14+CD16+ monocytes, monocyte-derived macrophages, synovitis, chemokine receptor expression, synovial hyperplasia, macrophage infiltration
MeSH terms
Adult, Aged, Cartilage, Articular, Chemotaxis, Leukocyte, Female, Humans, Macrophages, Male, Middle Aged, Monocytes, Synovial Fluid, Synovial Membrane, Case-Control Studies, Receptors, IgG, Disease Progression, Chemokine CCL2, Lipopolysaccharide Receptors, Receptors, Chemokine, Receptors, CCR5, Chemokines, CC, Osteoarthritis, Knee, Receptors, CCR1, Receptors, CCR2, Chemokine CCL3, Chemokine CCL4

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