Sulforaphane modulates macrophage polarization via JAK1/STAT1 inhibition to promote tendon repair in tendinopathy.

BACKGROUND

Imbalanced M1/M2 macrophage polarization is central to tendinopathy pathogenesis. Sulforaphane (SFN), a natural compound with anti-inflammatory properties, may modulate macrophage polarization.

METHODS

This study utilized a collagenase-induced mouse model of tendinopathy to evaluate the therapeutic effects of local SFN administration on tendinopathy in vivo. Furthermore, the effects of SFN on macrophage polarization were investigated in vitro, and RNA sequencing was used to explore the mechanisms by which SFN regulates macrophage polarization in vivo. Finally, an ex vivo human pathological tendon culture system was employed to explore the therapeutic effects of SFN on tendinopathic lesions.

RESULTS

In this study, we found that SFN modulated the polarization of M1 macrophages towards M2 macrophages, thereby effectively modulating the inflammatory response. RNA sequencing and Western blot analyses indicated that the effect of SFN was mediated through the JAK1/STAT1 signaling pathway. In a collagenase-induced mouse model of tendinopathy, local injection of SFN led to a significant improvement in tendon tissue structure, with the collagen matrix restoring its natural dense parallel arrangement. Furthermore, there was an increase in local M2 macrophages and a decrease in M1 macrophages, which promoted the resolution of inflammation. Finally, the immunomodulatory effect of SFN on macrophages was also validated in tendon tissue from patients with tendinopathy.

CONCLUSIONS

SFN can effectively alleviate tendinopathy by promoting the polarization of M1 macrophages towards M2 macrophages, an effect achieved through the inhibition of the JAK1/STAT1 signaling pathway, thereby providing a promising therapeutic approach for the treatment of tendinopathy.