Harvard Medical School, Boston, MA, USA.
Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Biochem Pharmacol. 2024 Jul;225:116273. doi: 10.1016/j.bcp.2024.116273. Epub 2024 May 8.
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.
肌肉骨骼疾病中的纤维性变化源于关节周围纤维性组织的异常积聚，导致活动受限、关节功能受损和生活质量下降。松弛素 (RLX) 通过加速胶原蛋白降解和抑制细胞外基质 (ECM) 的过度产生来减轻纤维化。此外，RLX 通过调节 TGF-β/Smads 信号通路来破坏肌成纤维细胞的激活，从而减少结缔组织纤维化。然而，随着越来越多的研究关注松弛素对皮肤、韧带、肌腱、软骨、关节囊、结缔组织和肌肉的影响，RLX 在肌肉骨骼病理学中的作用和影响正在显现。本综述描述了松弛素在肌肉骨骼系统中的作用以及其临床应用所面临的挑战。松弛素在体内和体外研究中均显示出在广泛管理肌肉骨骼纤维化方面的巨大潜力；然而，半衰期短和性别特异性反应等挑战可能会对临床应用构成障碍。
