# Increased synovitis and pro-inflammatory macrophage abundance are observed in the synovia of patients at risk of developing post-traumatic OA compared to those with established OA

## TL;DR

Early-stage osteoarthritis is marked by more synovial inflammation and pro-inflammatory macrophages compared to late-stage disease.

## Contribution

This study reveals that synovitis and pro-inflammatory macrophages are more prominent in early post-traumatic osteoarthritis.

## Key findings

- Synovitis is more prevalent and severe in early-OA compared to late-OA synovia.
- Early-OA synovia contains more macrophages, particularly those with pro-inflammatory (M1) phenotypes.
- Synovitis severity correlates with macrophage counts and both M1 and M2 markers.

## Abstract

Inflammation of the synovium (synovitis) is implicated in the onset, progression and clinical manifestation of osteoarthritis (OA), although its prevalence at different stages of the disease has yet to be definitively established. Synovial macrophages play a central role in synovitis and can demonstrate pro- and anti-inflammatory phenotypes. The pervasiveness and variation in phenotypic identity of macrophages in early- and late-OA synovia is unclear. In the present study we investigated the frequency and severity of synovitis and assessed macrophage phenotypes in synovia from patients with high risk of developing PTOA (deemed early-OA) or late-OA.

Synovial samples were collected from patients undergoing cell therapy treatment for early-OA or arthroplasty for late-OA. Synovitis was assessed using a semi-quantitative, histological scoring system. Macrophage abundance and phenotypic characteristics were assessed by immunohistochemistry and image analysis. Study parameters were compared between the early- and late-OA groups and correlated with demographic and clinical information.

Synovitis was more prevalent and generally more severe in early-OA synovia compared to late-OA synovia (effect size; d ​= ​0.76). There were more macrophages overall (d ​= ​1.04), with more demonstrating markers characteristic of a pro-inflammatory (M1) phenotype (d ​= ​0.86), in the early-OA cohort. Synovitis severity was significantly correlated with the total number of macrophages (ρ ​= ​0.47), and with the presence of both M1 (ρ ​= ​0.65) and M2 (ρ ​= ​0.49) macrophage markers (M2 typically considered to indicate an anti-inflammatory or wound-healing phenotype).

Our data suggest that synovial inflammation may play a greater role in the early stages of OA than in end-stage disease, and is at least partly mediated by synovial macrophages.