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Macrophages drive the inflammatory phase in experimental osteoarthritis

By Anna Montgomery, Niamh Fahy, Samuel Hamilton, Blair Eckman, Lucia De Almeida, Shingo Ishihara, Maximilian G Mayr, Shang Yang Chen, Gaurav Gadhvi, Carla Cuda, Anne-Marie Malfait, Yvonne Bastiaansen-Jenniskens, Deborah R. Winter

Posted 31 May 2020
bioRxiv DOI: 10.1101/2020.05.28.122408

Macrophages fulfill critical functions in maintaining tissue homeostasis in steady-state, as well as in inflammation and immune response. Inflammation is not considered a major driver of osteoarthritis (OA), but macrophages have been implicated in its pathogenesis. Here, we use two mouse models of experiment OA - collagenase-induced osteoarthritis (CIOA) and destabilization of the medial meniscus (DMM) - to quantify the immune cell infiltration into the knee joint during the early stages of disease. We find that the peak of inflammation occurs at day 3 in CIOA and is characterized by a transitory increase in neutrophils and monocytes and a longer-lived expansion of synovial macrophages. Macrophage sub-populations are disproportionally expanded with CX3CR1+ cells accounting for a larger proportion of the macrophage compartment. Transcriptional profiling demonstrates that synovial macrophages up-regulate inflammatory genes coinciding with peak inflammation and down-regulate genes associated with homeostasis and tissue-residence. Female mice exhibit a similar expansion of macrophages post-CIOA indicating that the inflammatory phase is not sex-specific. Finally, we find day 7 post-DMM is also characterized by increases in neutrophil, monocyte, and macrophage sub-population numbers. These results support a role for macrophages in early stages of OA through driving the inflammatory phase. Further investigation may elucidate potential targets for the prevention or attenuation of OA-associated cartilage damage. ### Competing Interest Statement The authors have declared no competing interest.

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