# Mechanical Stimulation of Equine Bone Marrow Mesenchymal Stromal Cell-Derived Cartilage-Like In Vitro Model Triggers Osteoarthritis Features

## TL;DR

This study created an in vitro model of cartilage that mimics osteoarthritis when subjected to mechanical stress, offering a new tool for studying the disease and testing treatments.

## Contribution

The study introduces a novel in vitro model of osteoarthritis using equine BM-MSCs and mechanical stimulation to replicate key disease features.

## Key findings

- Mechanical stimulation reduced cell proliferation and type II collagen levels in cartilage-like models.
- GAG content in the models decreased while GAG release increased after mechanical stress.
- Compression upregulated catabolic factors and inflammatory mediators, resembling OA progression.

## Abstract

Osteoarthritis (OA) affects millions of people globally,
causing
irreversible cartilage damage, chronic inflammation, and progressive
joint dysfunction. Similarly, horses can develop OA spontaneously
or due to their athletic careers, influenced by mechanical and biochemical
factors. Current treatments primarily focus on symptom relief without
promoting cartilage regeneration. In line with the 3Rs principles
(refine, reduce, replace), the development of in vitro OA models is essential for advancing new therapeutic approaches
against OA. In response to this need, the present study aimed to develop
an in vitro model of mechanically induced OA. Bone
marrow-derived mesenchymal stromal cells (BM-MSCs) were cultured in
a biomaterial scaffold and differentiated for 21 days using a chondrogenic
medium to produce cartilage-like in vitro models.
The cartilage-like in vitro models underwent mechanical
stimulation (compression) for 3 and 7 days at pressures sufficient
to induce injurious stress. BM-MSC-derived chondrocytes express the
transient receptor potential vanilloid-type 4 (TRPV4) channel and
are responsive to mechanical stimulation. Mechanical stimulation was
found to reduce cell proliferation without inducing cell death. The
overall protein levels of type II collagen drastically declined after
both 3 and 7 days of mechanical stimulation. Additionally, glycosaminoglycan
(GAG) content within the cartilage-like in vitro models
decreased, whereas GAG release into the supernatant increased following
mechanical stimulation. Ultimately, compression led to the upregulation
of catabolic factors and inflammatory mediators. In conclusion, this
model successfully replicates several key features of OA, making it
a valuable tool for investigating the disease’s mechanisms
and testing new therapeutic strategies.