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

Abstract

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.

Exploring lncRNA Expression Patterns in Patients With Hypertrophied Ligamentum Flavum

“…Past studies have demonstrated that collagen I and collagen III are representative fibrotic products [ 25 ]. TGF-β promotes collagen production and induces fibrosis in LF cells [ 26 - 28 ]. These results suggest that PARD3-AS1 may significantly affect the underlying processes and pathophysiology of LFH.…”

“…The blots were blocked with 5% skim milk and incubated overnight at 4°C with primary antibodies. These antibodies (Abcam, Cambridge, UK) were prepared in 5% bovine serum albumin as follows: collagen I (1:1,500, ab279711); collagen III (1:1,500, ab6310); transforming growth factor (TGF)-β1 (1:1,500, ab215715), and GAPDH (1:5,000, ab8245) [ 25 - 28 ].…”

MRI parameters predict central lumbar spinal stenosis combined with redundant nerve roots: a prospective MRI study

“…There was no difference between the groups. Several studies ( 27–29 ) have shown that ligamentum flavum hypertrophy is the main causative factor of central spinal stenosis and is involved in long-term chronic compression of the dural sac ( 5 , 30 ). RNRs due to ligamentum flavum hypertrophy-induced spinal stenosis are a chronic process with a high incidence of RNRs.…”