Altered Wnt and NF-<i>κ</i>B Signaling in Facet Joint Osteoarthritis: Insights from RNA Deep Sequencing

Abstract

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-κB 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-κB 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 A1 were decreased. These results suggest that Wnt and NF-κB 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.

The Role of Inflammation in the Pathogenesis of Osteoarthritis

“…Production of CCL7 from synoviocytes is enhanced by IL-17 [41]. Patients with facet joint osteoarthritis (n = 48) also demonstrated elevated CCL4 and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) compared to healthy controls (n = 10) [64]. The study showed that CCL4 and CCL4L2 expressions were involved in the canonical NF-κB signaling pathway.…”

Transcriptional analysis of long non-coding RNAs in facet joint osteoarthritis

“…Their subsequent functional study suggested that lncRNA uc.217 could regulate neurite outgrowth and lncRNA TNXA-PS1 could regulate Schwann cell migration. [19][20][21] In the current work, by using RNA deep sequencing, we identied a total of 37 488 lncRNAs in facet joints. By comparing the expression levels of these lncRNAs in patients with control facet joints and patients with FJOA, a total of 8506 differentially expressed lncRNAs were discovered.…”

Transcriptome sequencing reveals dynamic changes in matrix metalloproteinases in facet joint osteoarthritis

“…Identification of the most differentially expressed genes in FJOA. Previous transcriptome sequencing determined the expression levels of >19,000 genes in human facet joint tissues in both FJOA and control groups (15). To obtain a global view of the expression patterns of identified genes, the Heatmap function in the software platform R (v.2.13.0) was used to draw a heatmap of gene expression ( Fig.…”

“…Human facet joint tissues were collected from 48 patients with FJOA (FJOA group) and 10 healthy patients with vertebral fractures (control group) as previously described (15). Magnetic resonance imaging was applied to determine the degree of cartilage degeneration.…”

“…The expression of key molecules in the degenerative process of facet joints such as MMP13, tumor necrosis factor-a and interleukin-6 have also been identified (14). A previous study determined the molecular changes in FJOA by collecting human facet joint tissues from healthy controls and patients with FJOA and conducting transcriptome sequencing (15).…”