Abstract
BackgroundFibrosis is an important factor and process of ligamentum flavum hypertrophy. The expression of phosphodiesterase family (PDE) is related to inflammation and fibrosis. This article studied the expression of PDE in hypertrophic ligamentum flavum fibroblasts and investigated whether inhibition of PDE4 activity can play an anti-fibrotic effect.MethodsSamples of clinical hypertrophic ligamentum flavum were collected and patients with lumbar disc herniations as a control group. The collagenase digestion method is used to separate fibroblasts. qPCR is used to detect the expression of PDE subtypes, type I collagen (Col I), type III collagen (Col III), fibronectin (FN1) and transforming growth factor β1 (TGF-β1). Recombinant TGF-β1 was used to stimulate fibroblasts to make a fibrotic cell model and treated with Rolipram. The morphology of the cells treated with drugs was observed by Sirius Red staining. Scratch the cells to observe their migration and proliferation. WB detects the expression of the above-mentioned multiple fibrotic proteins after drug treatment. Finally, combined with a variety of signaling pathway drugs, the signaling mechanism was studied.ResultsMultiple PDE subtypes were expressed in ligamentum flavum fibroblasts. The expression of PDE4A and 4B was significantly up-regulated in the hypertrophic group. Using Rolipram to inhibit PDE4 activity, the expression of Col I and TGF-β1 in the hypertrophic group was inhibited. Col I recovered to the level of the control group. TGF-β1 was significantly inhibited, which was lower than the control group. Recombinant TGF-β1 stimulated fibroblasts to increase the expression of Col I/III, FN1 and TGF-β1, which was blocked by Rolipram. Rolipram restored the increased expression of p-ERK1/2 stimulated by TGF-β1.ConclusionThe expressions of PDE4A and 4B in the hypertrophic ligamentum flavum are increased, suggesting that it is related to the hypertrophy of the ligamentum flavum. Rolipram has a good anti-fibrosis effect after inhibiting the activity of PDE4. This is related to blocking the function of TGF-β1, specifically by restoring normal ERK1/2 signal.
Highlights
Hypertrophy of the ligamentum flavum (LF) is an important factor in lumbar spinal stenosis, causing pain and difficulty walking [1]
Hypertrophic group and control constituted the expression of phosphodiesterase family (PDE) family in fibroblasts (Fig. 1A)
The expression levels of other PDE subtypes vary among individuals, but there is no statistical difference (Table 2)
Summary
Hypertrophy of the ligamentum flavum (LF) is an important factor in lumbar spinal stenosis, causing pain and difficulty walking [1]. People hope to explore the causes of LF hypertrophy and find safe and efficient treatment strategies. Infiltrating macrophages secrete a large number of inflammatory factors and activate fibroblasts [4]. Stimulates the secretion and deposition of collagen fibers, which eventually causes the LF hypertrophy [5]. Inflammation and fibrosis are two important factors for LF hypertrophy [6]. Substances that exert anti-inflammatory and antifibrotic effects may be beneficial to the treatment of LF hypertrophy. Fibrosis is an important factor and process of ligamentum flavum hypertrophy. This article studied the expression of PDE in hypertrophic ligamentum flavum fibroblasts and investigated whether inhibition of PDE4 activity can play an antifibrotic effect
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