Potential role of the IL17RC gene in the thoracic ossification of the posterior longitudinal ligament

Int J Mol Med. 2019 May;43(5):2005-2014. doi: 10.3892/ijmm.2019.4130. Epub 2019 Mar 12.

Abstract

The thoracic ossification of the posterior longitudinal ligament (T‑OPLL) can cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. Our previous whole‑genome sequencing study first reported rs199772854 in the interleukin 17 receptor C (IL17RC) gene as a potentially pathogenic loci for T‑OPLL. The aim of the present study was to examine the effects of the IL17RC gene rs199772854A site mutation on osteogenesis by establishing a model of osteogenic differentiation. IL17RC gene mutation site and wild‑type site mouse embryonic osteoblast (3T3‑E1) models were constructed in order to induce the differentiation of the cells into osteoblasts. Whether the mutation site causes the abnormal expression of the IL17RC gene and osteogenic markers was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The IL17RC gene rs199772854A site mutation was demonstrated to play a biological role through the overexpression of its own gene, and also to significantly increase the expression levels of osteogenic markers. Furthermore, the mutation upregulated the expression of the key proteins, tumor necrosis factor receptor (TNFR)‑associated factor 6 (TRAF6) and nuclear factor (NF)‑κB, in the interleukin (IL)‑17 signaling axis. On the whole, the findings of this study suggest that the IL17RC gene rs199772854A loci mutation propels mouse embryonic osteoblasts towards osteogenic differentiation and may play an important role in the pathogenesis of T‑OPLL. The IL17RC gene may promote osteogenesis through the IL‑17 signaling pathway and may thus be involved in the process of ectopic osteogenesis in T‑OPLL.

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Cell Differentiation
  • Lentivirus / genetics
  • Longitudinal Ligaments / pathology*
  • Mice
  • Mutation / genetics
  • Ossification, Heterotopic / genetics*
  • Osteogenesis
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Interleukin-17 / genetics*
  • Thorax / pathology*

Substances

  • Receptors, Interleukin-17