Changes in Gene Expression of Discs from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Patients Compared to Traumatic/Degenerative Discs

May, Rahel D.; Frauchiger, D.A.; Albers, Christoph E.; Benneker, Lorin M.; Hofstetter, W.; Gantenbein, Benjamin (2019). Changes in Gene Expression of Discs from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Patients Compared to Traumatic/Degenerative Discs. In: TERMIS EU chapter meeting. Rhodes, Greece. 27th-31st May 2019.

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INTRODUCTION: Diffuse idiopathic skeletal hyperostosis (DISH) affects mostly mid-aged and elderly people. DISH is characterized by the formation of bone along the anterior spine. Further ossification of the outer intervertebral discs (IVD) can be observed [1]. However, the nucleus pulposus (NP) remains unaffected. We have recently shown, that the IVD cells are expressing BMP antagonists, which could lead to inhibition of bone formation for spinal fusion. In this study, we investigate the transcriptome of discs of the BMP pathway from DISH patients with traumatic or degenerative discs.

METHODS: Fresh DISH-IVDs and trauma or degenerated IVDs were obtained from patients undergoing spinal surgery (approved by the Ethics Committee of the Canton of Bern, CH). 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 & DISCUSSION: 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) were upregulated 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 down-regulated in two of the three DISH-IVDs (i.e., -21.9 ± 16.2-fold and -8.2 ± 4.2-fold, respectively).

CONCLUSIONS: 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.

ACKNOWLEDGEMENTS: Financial support was received from direct funds from the Clinical Trial Unit, Inselspital, Bern University Hospital, and by a grant of the Swiss Society of Orthopaedics and Traumatology to C. E. A.

REFERENCES

[1] Resnick D et al. 1978. AM J Roentgenol 131:1049-1053

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