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

Atousa Nourmahnad; Mohammad Javad Shariyate; Mohamad Khak; Mark W Grinstaff; Ara Nazarian; Edward K Rodriguez

doi:10.1016/j.bcp.2024.116273

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

Biochem Pharmacol. 2024 May 8:225:116273. doi: 10.1016/j.bcp.2024.116273. Online ahead of print.

Authors

Atousa Nourmahnad¹, Mohammad Javad Shariyate², Mohamad Khak², Mark W Grinstaff³, Ara Nazarian⁴, Edward K Rodriguez⁵

Affiliations

¹ Harvard Medical School, Boston, MA, USA.
² Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³ Department of Chemistry, Boston University, Boston, MA, USA.
⁴ Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan, Armenia.
⁵ Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: ekrodrig@bidmc.harvard.edu.

PMID: 38729446
DOI: 10.1016/j.bcp.2024.116273

Abstract

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.

Keywords: Joint; Musculoskseletal fibrosis; Range of motion; Relaxin; Treatment.

Publication types

Review

Abstract

Publication types

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