T-OPLL poses a major challenge for spinal surgeons. Although the exact cause of the disease is still unclear, it is generally believed that genetic factors have an important role in the development of the disease. Some scholars believe that the accumulation of harmful missense mutations in the human genome creates the genetic basis for various complex diseases [
22]. Whole genome sequencing identified a C > A mutation at the rs199772854 locus of the IL17RC gene. Disease progression is also affected by the gene expression in peripheral blood cells, with several genes reported to exhibit higher expression in the peripheral blood of OPLL patients compared to healthy controls [
9,
23].
In this study, peripheral blood of T-OPLL patients with or without an rs199772854 mutation was collected and analyzed to assess the role of the mutated gene locus. The results of ELISA and qPCR analysis demonstrated that the expression of IL17RC was significantly higher in the peripheral blood of T-OPLL patients carrying the rs199772854A mutation compared to patients without the mutation. IHC and WB were performed to determine IL17RC expression in patients with T-OPLL, and the results demonstrated that the expression of IL17RC protein was significantly higher in the T-OPLL patients with the mutation compared to those with the wild-type. Therefore, the rs199772854A site mutation may lead to overexpression of IL17RC. We also showed that there was no difference in the OPLL classification and JOA score between T-OPLL patients with and without the rs199772854A mutation. The possible association between the rs199772854A site mutation in IL17RC and the severity of the T-OPLL phenotypes requires larger-scale studies in the future.
The rs199772854 site of the IL17RC gene is located in the promoter region. An SNP in the promoter region can increase or reduce gene transcriptional activity by altering the binding efficiency of transcription factors to various sequence elements, thus interfering with the gene expression process and potentially leading to disease occurrence. However, the mechanism and role of IL17RC gene regulation during ectopic osteogenesis remains unclear. IL17RC may accelerate bone metabolism via the transforming growth factor-β signaling pathway [
24,
25]. The majority of studies suggest that IL17RC has a major role in disease pathogenesis through its function in the IL17 signaling axis. Some studies have shown that the IL17 axis affects bone formation and remodeling, and can also protect bone mass if bone loss occurs due to infection or hormonal imbalance [
26,
27]. In addition, the IL17 axis can induce osteoblastic differentiation of bone marrow-derived mesenchymal stem cells [
28]. It has become increasingly clear that inflammation-mediated imbalance in bone is a major feature of various bone diseases [
29]; this imbalance is caused by increases in various cytokines in the inflammatory tissue. As an inflammatory factor, IL17 RC are expressed on various cells, such as osteoblasts, chondrocytes, and fibroblasts [
30], and compression force can induces the expression of IL-17RC in osteoblast-like cells [
31,
32]. In addition, the differentiation of osteoclast precursors into osteoclasts is suppressed by IL17RC [
30]; IL17RC produced in response to compressive force may suppress osteoclastogenesis through the expression of OPG [
31]. Additionally, IL17RC stimulates the secretion of other factors such as IL-6, tumor necrosis factor (TNF)-α and IL-1β in osteoclasts, further aggravating the inflammation [
33].
The results of this study demonstrated that the expression of IL17RC in T-OPLL patients carrying an rs199772854A mutation was significantly higher in peripheral blood and tissues than in patients without the mutation. It is suggested that the rs199772854A site mutation can lead to overexpression of IL17RC and may induce pathological OPLL. However, this study lacks in-depth research and discussion on the mechanism by which IL17RC facilitates T-OPLL. In addition, due to the prevalence of T-OPLL disease is very rare, this study’s sample size is small. The association between heterotopic ossification and IL17RC requires further research.