Altered Wnt and NF-kappa B Signaling in Facet Joint Osteoarthritis: Insights from RNA Deep Sequencing

摘要

Facet joint osteoarthritis is common lumbar osteoarthritis characterized by facet joint cartilage degeneration. However, the molecular basis of facet joint osteoarthritis remains largely undetermined. In the current study, we collected facet joint tissue samples from 10 control patients and 48 patients with facet joint osteoarthritis (20 patients with moderate degeneration and 28 with severe degeneration). The control patients underwent internal fixation of the lumbar spine due to vertebral fracture. RNA deep sequencing was performed, and Bioinformatic tools were applied. Among top 30 enriched signaling pathways, we focused on two inflammation-related signaling pathways, Wnt and NF-kappa B signaling pathways. Subsequently, using the quantitative RT-PCR analysis, we confirmed that in Wnt signaling pathway, the mRNA levels of Dickkopf WNT Signaling Pathway Inhibitor 2 (DKK2), Sex-determining Region Y-box 17 (SOX17), MYC, Cyclin D1, Calcium/Calmodulin Dependent Protein Kinase II Alpha (CAMK2A), and Wnt Family Member 11 and 5 were increased in facet joint osteoarthritis, while the mRNA levels of WNT Inhibitory Factor 1, Casein Kinase 1 Alpha 1, Transcription Factor 7/Lymphoid Enhancer Binding Factor 1 (TCF7/LEF1), and VANGL Planar Cell Polarity Protein 2 were decreased. In NF-kappa B signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein Al were decreased. These results suggest that Wnt and NF-kappa B signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.