Abstract
Background Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. Objective To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. Methods A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. Results Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. Conclusion Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration.
Highlights
Intervertebral disc degeneration is the underlying basic pathological process of a series of spinal degenerative diseases [1]; the specific pathophysiological mechanism involved remains unclear
Compared with that in the sham group, the intervertebral disc tissue in the model group was mainly composed of type I collagen, with a disordered annulus fibrosus and an increased number of breaks and obvious signs of degeneration
Treatment with sIL-13Rα2-Fc significantly decreased the extent of intervertebral disc degeneration in rats, which was characterized by the dominant expression of type II collagen, an evenly arranged annulus e blank group e sham group e model group e group treated with Sil-13rα-fc
Summary
Intervertebral disc degeneration is the underlying basic pathological process of a series of spinal degenerative diseases (such as disc herniation, spinal canal stenosis, spondylolisthesis, spinal instability, and neuropathy) [1]; the specific pathophysiological mechanism involved remains unclear. To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways Compared with those in the model group, the mRNA expression levels of Rnux, Sod, and Tnfaip in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt, Fgf, Celsr, and Adamts were downregulated; these results were verified by realtime fluorescence quantitative PCR. SIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts, maintaining the dynamic equilibrium of the ECM and delaying intervertebral disc degeneration Adamts may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts, maintaining the dynamic equilibrium of the ECM and delaying intervertebral disc degeneration
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