scholarly journals EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs

2021 ◽  
Vol 11 (9) ◽  
pp. 4072
Author(s):  
Benjamin Gantenbein ◽  
Rahel D. May ◽  
Paola Bermudez-Lekerika ◽  
Katharina A. C. Oswald ◽  
Lorin M. Benneker ◽  
...  

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.

2015 ◽  
Vol 35 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Chencheng Feng ◽  
Huan Liu ◽  
Yang Yang ◽  
Bo Huang ◽  
Yue Zhou

Intervertebral disc degeneration (IDD) is a widely recognized contributor to low back pain (LBP). The Prevention or reversal of IDD is a potential treatment for LBP. Unfortunately, current treatments for IDD are aimed at relieving symptoms rather than regenerating disc structure or function. Recently, the injection of growth factors and mesenchymal stem cell (MSC) transplantation have been shown to be promising biological therapies for IDD. Growth factors stimulate the proliferation of and matrix synthesis by intervertebral disc (IVD) cells, leading to the regeneration of degenerative discs. Growth factors, hypoxia and co-culture with nucleus pulposus (NP) cells induce MSCs to differentiate toward an NP-like phenotype, which can increase the number of functional cells in the IVD or enhance the function of endogenous disc cells to facilitate IVD regeneration. Therefore, the emerging roles of growth factors in IVD regeneration have piqued the interest of researchers. Growth factors including transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1) and growth and differentiation factor-5 (GDF-5), among others, have been demonstrated to enhance anabolism in IVD cells and to induce NP-like differentiation of MSCs. However, the injection of TGF, IGF and FGF into human IVDs may induce unwanted blood vessel ingrowth, which accelerates the process of IDD, the injection of GDF-5 may not have the same effect. This finding suggests that GDF-5 is a preferable growth factor for use in IDD treatment compared with TGF, IGF and FGF. The GDF-5 gene is one of the few growth factor genes that have been found to be associated with IDD thus far; moreover, the GDF-5 gene defects lead to collagen and proteoglycan abnormalities in discs in mice, suggesting that GDF-5 contributes to the structural and functional maintenance of the IVD. This review is focused on the functions of GDF-5 in the IVD and on the association between GDF-5 and a genetic predisposition to IDD. The effects of GDF-5 on IVD regeneration and on MSC differentiation are also discussed. GDF-5 plays a crucial role in the pathogenesis of IDD and is a promising therapeutic agent for IDD. Additionally, stem cell transplantation has been shown to be a promising biological therapy for IDD.


Neurosurgery ◽  
2006 ◽  
Vol 58 (6) ◽  
pp. 1027-1039 ◽  
Author(s):  
Joji Inamasu ◽  
Bernard H. Guiot ◽  
Donald C. Sachs

Abstract SIGNIFICANT PROGRESS HAS been achieved in basic research during the past decade on the pathogenesis of ossification of the posterior longitudinal ligament (OPLL), a multifactorial disease in which complex genetic and environmental factors interact. A review of the literature was conducted to update recent findings on the biology, epidemiology, natural history, and related diseases of OPLL. Gene analysis studies found specific polymorphisms that may be associated with OPLL in several collagen genes, which encode for extracellular matrix proteins. Polymorphisms in the nucleotide pyrophosphate gene, which is involved in regulation of calcification in chondrocytes, may also be associated with OPLL. However, the results of the gene analysis studies have not always been consistent. Involvement of many growth factors and cytokines, including bone morphogenic proteins and transforming growth factor-β, has been demonstrated in various histochemical and cytochemical analyses. Several transcription factors involved in cellular differentiation may also have a role. Recent epidemiological studies reaffirmed an earlier finding that diabetes mellitus is a distinct risk factor for OPLL. The long-term follow-up studies of OPLL patients are disclosing the natural history, as well as the frequency and rate of progression, of OPLL after surgical intervention. Further knowledge on the factors responsible for progression of OPLL may predict its behavior in each patient, and treatment may be tailored accordingly. The coexistence of OPLL with other diseases of ectopic ossification of the spine, such as ossification of the ligamentum flavum and diffuse idiopathic skeletal hyperostosis, is not uncommon. Scientific breakthrough in those diseases may, in turn, give insights into the pathogenesis of OPLL.


2011 ◽  
Vol 63 (10) ◽  
pp. 3022-3031 ◽  
Author(s):  
Cassie M. Tran ◽  
Harvey E. Smith ◽  
Aviva Symes ◽  
Laure Rittié ◽  
Bernard Perbal ◽  
...  

2019 ◽  
Vol 38 (2) ◽  
pp. 438-449 ◽  
Author(s):  
Sajjad Ashraf ◽  
Kenny Chatoor ◽  
Jasmine Chong ◽  
Robert Pilliar ◽  
Paul Santerre ◽  
...  

2018 ◽  
Vol 75 (5) ◽  
pp. 287-294
Author(s):  
Michael Scharl

Zusammenfassung. Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft dar.


Sign in / Sign up

Export Citation Format

Share Document