Macrophage phenotypes and monocyte subsets after destabilization of the medial meniscus in mice

Lizette Utomo, Niamh Fahy, Nicole Kops, Sandra T. van Tiel, Jan Waarsing, Jan A.N. Verhaar, Pieter J.M. Leenen, Gerjo J.V.M. van Osch*, Yvonne M. Bastiaansen-Jenniskens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Macrophages play an important role in the development and progression of osteoarthritis (OA). The aim of this study was to identify macrophage phenotypes in synovium and monocyte subsets in peripheral blood in C57BL/6 mice by destabilizing the medial meniscus (DMM), and the association of macrophage subsets with OA features. DMM, sham, and non-operated knees were histologically assessed between 1 and 56 days for macrophage polarization states by immunohistochemistry (IHC), cartilage damage, synovial thickening, and osteophytes (n = 9 per timepoint). Naive knees (n = 6) were used as controls. Monocyte and polarized synovial macrophage subsets were evaluated by flow cytometry. CD64 and CD206 levels on IHC were higher at early timepoints in DMM and sham knees compared to naive knees. iNOS labeling intensity was higher in DMM and sham knees than in naive knees from d3 onwards. CD163 expression was unaltered at all timepoints. Even though macrophage polarization profiles were similar in DMM and sham knees, only in DMM knees the presence of iNOS and CD206 associated with synovial thickness, and CD163 staining inversely correlated with osteophyte presence. At day 14, monocyte subset distribution was different in peripheral blood of DMM mice compared with sham mice. In conclusion, monocyte subsets in blood and synovial macrophage phenotypes vary after joint surgery. High levels of iNOS+, CD163+, and CD206+ cells are found in both destabilized and sham-operated knees, and coexistence with joint instability may be a requirement to initiate and exacerbate OA progression.

Original languageEnglish
Pages (from-to)2270-2280
Number of pages11
JournalJournal of Orthopaedic Research
Volume39
Issue number10
DOIs
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
This study was financially supported by the Dutch Arthritis Foundation (grant nos. 13‐3‐302, LLP11, and 18‐1‐202) and an Erasmus MC Fellowship. The authors would also like to thank Anne Kozijn (UMC Utrecht/TNO Leiden) for her help with the DMM model and Bastiaan Tuk (Dept. of Plastic Surgery, Erasmus MC) for providing resources for the immunohistological stainings. This study was done within the postgraduate school Molecular Medicine, Erasmus MC, University Medical Center, The Netherlands.

Funding Information:
This study was financially supported by the Dutch Arthritis Foundation (grant nos. 13-3-302, LLP11, and 18-1-202) and an Erasmus MC Fellowship. The authors would also like to thank Anne Kozijn (UMC Utrecht/TNO Leiden) for her help with the DMM model and Bastiaan Tuk (Dept. of Plastic Surgery, Erasmus MC) for providing resources for the immunohistological stainings. This study was done within the postgraduate school Molecular Medicine, Erasmus MC, University Medical Center, The Netherlands.

Publisher Copyright:
© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

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