Changes in gene expression of intervertebral discs from diffuse idiopathic skeletal hyperostosis (DISH) patients compared to traumatic/degenerative intervertebral discs

Abstract

Introduction: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by the formation of bone along the anterior spine. Further ossification of the outer intervertebral discs (IVD) can be observed. However, the nucleus pulposus (NP) remains unaffected. We investigated the phenotype of disc cells of DISH patients and why the IVD resists ossification. Methods: Cells were isolated from IVD tissue of DISH and control patients. TGFβ BMP signaling pathway genes were compared by qPCR. IVDs of three DISH patients were tested against three control patients (same disc level and similar age). IVD of two donors could be separated in NP, annulus fibrosus (AF) and cartilaginous endplate (CEP), one donor was investigated without discriminated IVD tissue. Results: In six of the seven comparisons a mean up-regulation of Interleukin 6 (IL-6) was detected (mean ± SEM of all comparisons: 88.8 ± 79.4-fold in DISH-IVD compared to controls). Early Growth Response 2 (EGR2) and Insulin-like Growth Factor 1 (IGF1) up-regulated in DISH-IVD donors (i.e., 20.5 ± 12.4-fold and 19.0 ± 19.5-fold, respectively). The two Growth and Differentiation Factors 5 and 6 (GDF5 and 6) were downregulated in two of the three DISH-IVDs (i.e., -21.9 ± 16.2-fold and -8.2 ± 4.2-fold, respectively). Conclusion: Most interestingly, the DISH-IVD cells showed a considerable change in IGF1 and IL-6. IGF1 was already determined as a serum marker for rheumatic diseases, such as DISH. These results are unexpected considering the fact that the ossification occurs in the neighboring ligaments and enthesis leaving the inner part of the IVD macroscopically unaffected.