# Comparative Effects of Dexamethasone and ASC Secretome in an Ex Vivo Osteoarthritis Co-Culture Model

## TL;DR

This study compares dexamethasone and stem cell secretome effects on joint tissues in an osteoarthritis model, finding that dexamethasone reduces inflammation more effectively.

## Contribution

The study introduces an ex vivo co-culture model to compare established and emerging osteoarthritis therapies.

## Key findings

- Dexamethasone significantly reduced inflammatory markers in both cartilage and synovial membrane.
- Stem cell secretome had limited anti-inflammatory effects but modulated matrix remodeling markers.
- Both treatments reduced metalloprotease activity, with dexamethasone showing broader effects.

## Abstract

Osteoarthritis is a common degenerative joint disease that still lacks effective treatments able to modify its progression. In this study, we used an experimental model that reproduces key features of the diseased joint by culturing cartilage and synovial membrane under controlled conditions. We compared the effects of dexamethasone, a widely used anti-inflammatory drug, with factors released by stem cells, collectively referred to as the secretome, and evaluated inflammation-related signals and the activity of enzymes involved in tissue remodeling. Dexamethasone effectively reduced inflammatory mediators in both cartilage and synovial membrane. The stem cell secretome showed more limited effects, mainly modulating matrix remodeling markers. These findings confirm the usefulness of this experimental model for comparing established and emerging therapies and support its application to investigate how new stem cell-based approaches may act on joint tissues.

Osteoarthritis (OA) is a multifactorial disease characterized by inflammation, extracellular matrix remodeling, and joint degeneration, and it still lacks disease-modifying treatments. Here, we applied an ex vivo OA model based on transwell co-cultures of cartilage and synovial membrane explants harvested from OA patients to compare the effects of adipose-derived stem/stromal cell (ASC) conditioned medium (CM) with dexamethasone (DEX), a clinically used corticosteroid. Explants were treated for 48 h with 100 nM DEX, CM derived from 5 × 105 ASCs, or left untreated. Outcomes included gene and protein expression of key mediators, metalloprotease and aggrecanase activities, and nitric oxide release. DEX significantly reduced inflammatory markers (e.g., PTGS, IL-1β, and IDO) and VEGF expression in both tissues, while CM did not elicit consistent anti-inflammatory effects. Regarding matrix remodeling, both treatments reduced metalloprotease activity, with DEX modulating MMP3 and MMP13 expression in both tissues and CM reducing only MMP3 expression in cartilage while presenting high levels of TIMP-1. These results confirm the robustness of the model, demonstrated by reproducible responses to DEX and its high-throughput potential, and underscore the need for mechanistic studies to optimize novel biotherapeutics.