Lumbar Disc Degeneration is Facilitated by MiR-100-Mediated FGFR3 Suppression

Abstract

Background/Aims: The pathogenesis of lumbar disc degeneration (LDD) involved activation of matrix metalloproteinase 13 (MMP13) by differential expression of fibroblast growth factor receptor 1 (FGFR1) and FGFR3. Nevertheless, the molecular regulation of FGFR1 and FGFR3 in the lumber disc cells remains elusive. Methods: We examined the FGFR1 and FGFR3 levels and microRNAs (miRNAs) levels in the resected LDD discs, compared to the traumatized, non-LDD discs. We analyzed the binding of miR-100 to the 3′UTR of FGFR3 mRNA and its effects on FGFR3 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-100 levels in a human nucleus pulposus SV40 cell line (HNPSV), and examined the effects on the expression of FGFR3 and MMP13, by RT-qPCR, Western blot and ELISA. Results: The levels of FGFR1 and miR-100 were significantly higher, while the levels of FGFR3 were significantly lower, in LDD discs, compared to the control non-LDD discs. The levels of FGFR3, but not the levels of FGFR1, inversely correlated with the levels of miR-100. Moreover, miR-100 was found to bind to the 3'UTR of FGFR3 mRNA to prevent its translation. In miR-100-modified HNPSV cells, we found that miR-100 decreased FGFR3 levels, and increased MMP13 levels. Conclusion: miR-100 may activate MMP13 through 3′UTR-suppressoin of FGFR3 mRNA to facilitate development of LDD.

Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR‐26a‐5p suppresses Smad1 to regulate disc homeostasis

“…Also, miRNAs were thought to function in disc degeneration by regulating extracellular matrix (ECM) degradation and NP cell proliferation and apoptosis. Several studies have demonstrated that miRNAs participate in disc degeneration by targeting matrix metalloproteinase like matrix metalloproteinase‐13 (MMP13), matrix metalloproteinase‐14 (MMP14) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), which contribute to the breakdown of extracellular matrix of discs . Besides direct regulation of the matrix‐degrading enzymes, miRNAs also target the upstream genes regulating ECM degradation, including Runt‐related transcription factor 2 (Runx2) and growth differentiation factor 5 (GDF5) .…”

N-Cadherin-Mediated Activation of PI3K/Akt-GSK-3β Signaling Attenuates Nucleus Pulposus Cell Apoptosis Under High-Magnitude Compression

“…Intervertebral disc degeneration (IDD) is a disease with high incidence of crowd worldwide [1, 2]. Currently, biological regeneration of IDD remains a difficult challenge for basic researchers and clinicians [3].…”

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

“…Due to the serious impacts of intervertebral disc degeneration (IDD) on the health care system and patients’ life quality, an increasing number of researchers is exploring its underlying mechanisms and seeking to develop effective treatments (IDD) [1, 2]. Despite numerous breakthroughs in this field in the past decades [3, 4], the many unknowns about disc degeneration require further investigation.…”