# Molecular mediators of motion: RNA–RBP networks in exercise-induced osteoarthritis protection

## TL;DR

Exercise protects joints from osteoarthritis by changing RNA and protein interactions that help maintain joint health.

## Contribution

This paper reviews how exercise changes RNA-RBP networks to protect against osteoarthritis and suggests new treatment possibilities.

## Key findings

- Exercise modulates RNA-RBP networks to enhance matrix anabolism in joints.
- RNA-RBP interactions suppress synovial inflammation and delay OA progression.
- Exercise-induced RBP rewiring inhibits chondrocyte senescence and supports joint homeostasis.

## Abstract

Osteoarthritis (OA) is a relatively common chronic degenerative disease of joints that was originally considered an imbalance between mechanical loads and tissue repair. Emerging evidence indicates that exercise confers protection not merely through mechanical loading, but also by acting as a systemic regulator of RNA metabolism. This modulation mainly happens by regulating RNA–RNA-binding protein interaction networks that can regulate joint homeostasis and delay the OA process. This article is a review of current understanding of how physical activity alters networks of RNA–RNA-binding proteins (RBPs) in different joint-related tissues, such as cartilage, synovium, skeletal muscle, and systemic circulation, and changes the metabolic and inflammatory pathways necessary for joint health. The article will examine molecular mechanisms by which exercise induces RNA metabolism reprogramming and protection from OA. It also studies the promising prospects of RNA–RBP networks in early detection of OA and targeting innovative treatment strategies. By combining what we know about RNA–RBP interaction with exercise physiology, this overview could clear the way to personalized exercise interventions and novel RNA-targeted therapies for OA.

Exercise rewires the RNA–RBP interactome to protect against osteoarthritis. Mechanical loading signals (e.g., Piezo1) initiate a protective signaling cascade that remodels RNA–RBP networks across joint tissues. This systemic modulation orchestrates three key protective mechanisms: enhancing matrix anabolism, suppressing synovial inflammation, and inhibiting chondrocyte senescence, collectively restoring joint homeostasis.Infographic illustrating how mechanical loading signals from exercise influence chondrocytes in knee joints, triggering Piezo1-mediated calcium influx and rewiring RNA-RBP regulatory networks to support matrix homeostasis, reduce synovial inflammation, control cell fate, and enable muscle-bone crosstalk, ultimately promoting joint homeostasis and osteoarthritis protection.

Exercise rewires the RNA–RBP interactome to protect against osteoarthritis. Mechanical loading signals (e.g., Piezo1) initiate a protective signaling cascade that remodels RNA–RBP networks across joint tissues. This systemic modulation orchestrates three key protective mechanisms: enhancing matrix anabolism, suppressing synovial inflammation, and inhibiting chondrocyte senescence, collectively restoring joint homeostasis.