# The use of molecular cues to regenerate musculoskeletal tissues

## TL;DR

This paper reviews how molecular signals can be used to regenerate musculoskeletal tissues like bone and cartilage, offering new therapeutic strategies for tissue repair.

## Contribution

The paper provides a comprehensive review of shared and tissue-specific molecular cues in musculoskeletal regeneration, highlighting potential therapeutic targets.

## Key findings

- Molecular regulators like growth factors and microRNAs play key roles in musculoskeletal tissue regeneration.
- Pathways such as TGF-β and NF-κB can either promote healing or cause fibrosis depending on their modulation.
- Targeting these molecular cues with therapies like microRNA replacement or growth factor delivery could enhance tissue repair.

## Abstract

Musculoskeletal tissues, including bone, tendon, cartilage, and muscle, are vital for movement and structural support, yet, their repair after injury remains a significant clinical challenge. Their regeneration relies on complex molecular signaling that regulates inflammation, repair, and remodeling. Understanding these cues, offers opportunities to design targeted therapeutic strategies.

This review summarizes current evidence on molecular regulators of musculoskeletal tissue regeneration with emphasis on both shared and tissue-specific mechanisms across bone, tendon, cartilage and muscle. Key molecular cues include growth factors, cytokines, extracellular matrix-derived signals, and non-coding RNAs, particularly microRNAs. Critical pathways such as TGF-β, NF-κB, FGF, and YAP/TAZ can either promote healing or drive pathological fibrosis depending on their modulation. This review discusses therapeutic strategies targeting these molecular cues, including microRNA replacement therapies, small molecules, growth factor delivery, and pathway-specific inhibitors or activators.

Understanding how these molecular cues and pathways function and interact to regulate healing and regeneration offers valuable insight into tissue-specific and cross-tissue repair strategies. These advances may support the development of targeted therapies to enhance musculoskeletal regeneration and functional recovery. Furthermore, future research should focus on integrating these molecular insights with biomaterial and mechanobiological approaches to develop next-generation regenerative interventions.