Decorin: a potential therapeutic candidate for ligamentum flavum hypertrophy by antagonizing TGF-β1

Ligamentum flavum hypertrophy (LFH) is the main physiological and pathological mechanism of lumbar spinal canal stenosis (LSCS). The specific mechanism for LFH has not been completely clarified. In this study, bioinformatic analysis, human ligamentum flavum (LF) tissues collection and analysis, and in vitro and in vivo experiments were conducted to explore the effect of decorin (DCN) on LFH pathogenesis. Here, we found that TGF-β1, collagen I, collagen III, α-SMA and fibronectin were significantly upregulated in hypertrophic LF samples. The DCN protein expression in hypertrophic LF samples was higher than that in non-LFH samples, but the difference was not significant. DCN inhibited the expression of TGF-β1-induced fibrosis-associated proteins in human LF cells, including collagen I, collagen III, α-SMA, and fibronectin. ELISAs showed that TGF-β1 can upregulate PINP and PIIINP in the cell supernatant, and this effect was inhibited after DCN administration. Mechanistic studies revealed that DCN suppressed TGF-β1-induced fibrosis by blocking the TGF-β1/SMAD3 signaling pathway. In addition, DCN ameliorated mechanical stress-induced LFH in vivo. In summary, our findings indicated that DCN ameliorated mechanical stress-induced LFH by antagonizing the TGF-β1/SMAD3 signaling pathway in vitro and in vivo. These findings imply that DCN is a potential therapeutic candidate for ligamentum flavum hypertrophy. Spinal health: Keeping a key ligament elastic A protein called decorin offers a potential therapy for ligamentum flavum hypertrophy (LFH), stiffening of the ligament inside the spinal canal that connects vertebrae. In LFH, fibrosis (deposition of extra collagen) thickens and stiffens the ligament, reducing the space in the spinal column, thereby compressing nerves and causing loss of mobility. Yang Liu and Hua Wu at Huazhong University of Science and Technology in Wuhan, China, investigated whether decorin, known to combat fibrosis in other contexts, could help treat LFH. Treating LF cells with decorin decreased levels of proteins associated with fibrosis. Testing in a rodent model of LFH showed that treatment with decorin reduced ligament thickness and the amount of collagen. Further testing indicated that decorin suppresses signaling that leads more collagen to be laid down. These results suggest a potential treatment approach for LFH.