Glycyrrhizin suppresses fatty infiltration following rotator cuff tear in mice.

Abstract

BACKGROUND: Rotator cuff tear (RCT)-induced muscle degeneration is a serious medical issue and an effective treatment is lacking. Glycyrrhizin (GL) may inhibit lipid accumulation in cancer cells, but its effect on musculoskeletal disorders remains unknown. The aim of this study was to investigate the effects of GL on muscle degeneration following RCT. METHODS: Fibro-adipogenic progenitor cells (FAPs) were cultured in adipogenesis induction medium with or without GL treatment, followed by Oil Red O and perilipin staining to assess adipogenic differentiation and lipid accumulation. Female C57BL/6 mice (10-week-old) were used (n = 10 for each group) to explore the antiadipogenic properties of GL in vivo. The rotator cuff was transected, the proximal humerus was excised, and the suprascapular nerve was denervated to induce degeneration of the rotator cuff muscles, creating a model of rotator cuff degeneration. Adipose infiltration was assessed through histological analysis by comparing GL-treated, nontreated, and sham-operated control groups. Differences in fibrosis progression, muscle weight, and mRNA expression of adipogenic and fibrotic markers were examined. RESULTS: When FAPs were induced adipogenic differentiation, lipid accumulation was significantly reduced in the GL-treated group compared to the control group (P < .001). Histological examination at 4 weeks post-RCT showed severe fatty infiltration of the supraspinatus (SSP), infraspinatus (ISP), and subscapularis muscles in the RCT group (P < .001, P < .001, P < .001). However, GL treatment significantly suppressed RCT-associated fatty infiltration of the SSP and ISP muscles (P < .001, P = .003). Quantitative polymerase chain reaction showed that GL treatment significantly downregulated the mRNA expression of adipogenic differentiation markers in the SSP (P = .019) and ISP (P = .002) muscles compared with the untreated RCT group. However, GL treatment did not affect muscle fibrosis (P = .998, P = .618, P = .963) and weight (P = .176, P = .891, P = .872) compared with the untreated RCT group. CONCLUSION: GL suppressed the adipogenic differentiation of FAPs and fatty infiltration in a mouse model of RCT, suggesting a potential role for GL in RCT treatment.