Relaxin as a treatment for musculoskeletal fibrosis: What we know and future directions

Fibrotic changes in musculoskeletal diseases arise from the abnormal buildup of fibrotic tissue around the joints, leading to limited mobility, compromised joint function, and diminished quality of life. Relaxin (RLX) attenuates fibrosis by accelerating collagen degradation and inhibiting excessive extracellular matrix (ECM) production. Further, RLX disrupts myofibroblast activation by modulating the TGF-β/Smads signaling pathways, which reduces connective tissue fibrosis. However, the mechanisms and effects of RLX in musculoskeletal pathologies are emerging as increasing research focuses on relaxin's impact on skin, ligaments, tendons, cartilage, joint capsules, connective tissues, and muscles. This review delineates the actions of relaxin within the musculoskeletal system and the challenges to its clinical application. Relaxin shows significant potential in both in vivo and in vitro studies for broadly managing musculoskeletal fibrosis; however, challenges such as short biological half-life and sex-specific responses may pose hurdles for clinical use.