# Cell-integrated serum-induced signalling patterns can differentiate between hand and knee osteoarthritis patients

## TL;DR

This study shows that serum from hand and knee osteoarthritis patients causes different cell signaling patterns, suggesting distinct biological mechanisms for each type of OA.

## Contribution

The study introduces a method to differentiate hand and knee osteoarthritis based on serum-induced cell signaling patterns.

## Key findings

- Hand OA serum induces high MAPK-related AP1 activity, while knee OA serum induces SRE, ISRE, and SOX9 activity.
- Principal component analysis clearly separates hand OA and knee OA into distinct clusters.
- No distinct subtypes were identified within either hand or knee OA groups.

## Abstract

OA is a very heterogeneous disease. Here, we aimed to differentiate OA patients based on their serum-induced cell-integrated signalling patterns.

In order to monitor the activity of different cellular homeostasis-regulating pathways in response to patient serum, we analysed the response of human OA serum samples to 16 cell-based transcription factor luciferase reporter assays. In this study we compared serum samples from 55 patients with knee OA, 56 patients with hand OA and 42 healthy controls.

Differential serum-induced pathway activity was observed between samples from healthy controls, knee OA and hand OA patients: serum of hand OA patients induced high MAPK-related AP1 activity whereas serum of knee OA patients induced more SRE, ISRE and SOX9 activity, which is related to ELK1-SRF, STAT1-STAT2 and SOX9 activity, respectively. Principal component analysis revealed that these differences differentiate hand OA from knee OA. Both hand and knee OA clustered clearly in two different endotypes each, but no principle component could be identified of these subtypes within either the hand OA or the knee OA sample group.

This study demonstrates that serum from hand OA and knee OA patients evokes diverse cellular signalling patterns that differentiates hand OA, knee OA and healthy controls. This underlines that the pathomolecular mechanisms of OA are likely significantly different between hand and knee OA, a finding that could lead to new insight into the pathobiology of OA endotypes and joint-specific therapies.