Abstract
Diffuse idiopathic skeletal hyperostosis (DISH) is characterised by ectopic ossification along the anterior spine and the outer intervertebral discs (IVD). However, the centre of the IVD, i.e., the nucleus pulposus, always remains unaffected, which could be due to the inhibition of the bone morphogenetic protein (BMP) pathway. In this study, we investigated the transcriptome for the BMP pathway of DISH-IVD cells versus disc cells of traumatic or degenerative discs. The disc cells originated from nucleus pulposus (NP), annulus fibrosus (AF) and from cartilaginous endplate (CEP) tissue. Here, ninety genes of the transforming growth factor β-BMP signalling pathway were screened by qPCR. Furthermore, the protein expression of genes of interest was further investigated by immune-staining and semi-quantitative microscopy. IVDs of three DISH patients were tested against three control patients (same disc level and similar age). Early Growth Response 2 (EGR2) and Interleukin 6 (IL6) were both significantly up-regulated in DISH-IVD cells compared to controls (12.8 ± 7.6-fold and 54.0 ± 46.5-fold, respectively, means ± SEM). Furthermore, Insulin-like Growth Factor 1 (IGF1) tended to be up-regulated in DISH-IVD donors, i.e., 174.13 ± 120.6-fold. IGF1 was already known as a serum marker for DISH and other rheumatoid diseases and is confirmed here to play a possible key role in DISH-IVD.
Highlights
Diffuse idiopathic skeletal hyperostosis (DISH), known as Forestier’s disease, was first described by Forestier and Rotes-Querol in 1950 [1]
Insulin-like Growth Factor 1 (IGF1) tended to be up-regulated in DISH-intervertebral discs (IVD) donors (174.1 ± 120.6-fold, p = 0.1704), this was non-significant
Growth and Differentiation Factor 5 (GDF5) and GDF6 both tended to be down-regulated in the DISH-IVDs
Summary
Diffuse idiopathic skeletal hyperostosis (DISH), known as Forestier’s disease, was first described by Forestier and Rotes-Querol in 1950 [1] The authors characterised this disorder by spinal stiffness, osteophytosis, and aberrant new-bone formation along the spine’s anterior lateral aspect. The incidence of DISH, remains unknown, but it seems that factors of metabolic, endocrine, genetic, and epigenetics seem to be important in the development of this condition [4,7]. This disease mainly affects the elderly and is more frequent in men (65%) than in women, and the prevalence increases with age (48–85) [8,9]. The disease is often co-diagnosed with osteoarthritis [10,11]
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