Diabetes mellitus as a risk factor for intervertebral disc degeneration: a critical review

2019 ◽  
Vol 28 (9) ◽  
pp. 2129-2144 ◽  
Author(s):  
Kalliopi Alpantaki ◽  
Alkisti Kampouroglou ◽  
Christos Koutserimpas ◽  
Grigoris Effraimidis ◽  
Alexander Hadjipavlou
2009 ◽  
Vol 11 (6) ◽  
pp. 741-748 ◽  
Author(s):  
Ho-Yeon Won ◽  
Jong-Beom Park ◽  
Eun-Young Park ◽  
K. Daniel Riew

Object Diabetes mellitus is thought to be an important etiologic factor in intervertebral disc degeneration. It is known that notochordal cells gradually disappear from the nucleus pulposus (NP) of the intervertebral disc with age by undergoing apoptosis. What is not known is whether diabetes has an effect on apoptotic rates of notochordal cells. The purpose of this study was to investigate the effect of hyperglycemia on apoptosis of notochordal cells and intervertebral disc degeneration in age-matched OLETF (diabetic) and LETO (control) rats. Methods Lumbar disc tissue (L1–2 through L5–6), including cranial and caudal cartilaginous endplates, was obtained from 6- and 12-month-old OLETF and LETO rats (40 rats, 10 in each of the 4 groups). The authors examined the NP using TUNEL, histological analysis, and Western blot for expression of matrix metalloproteinase (MMP)–1, -2, -3, and -13, tissue inhibitor of metalloproteinase (TIMP)–1 and -2, and Fas (apoptosis-related protein). The apoptosis index of notochordal cells was calculated. The degree of transition of notochordal NP to fibrocartilaginous NP was classified on a scale ranging from Grade 0 (no transition) to Grade 4 (transition > 75%). The degree of expression of MMP-1, -2, -3, and -13, TIMP-1 and -2, and Fas was evaluated by densitometry. Results At 6 and 12 months of age, OLETF rats showed increased body weight and abnormal 2-hour glucose tolerance tests compared with LETO rats. The apoptosis index of notochordal cells was significantly higher in the OLETF rats than in the LETO rats at both 6 and 12 months of age. The degree of transition of notochordal NP to fibrocartilaginous NP was significantly higher in the OLETF rats than in the LETO rats at 6 and 12 months of age. The expression of MMP-1, -2, -3, and -13, TIMP-1, and Fas was higher in the OLETF rats at 6 and 12 months of age. The expression of TIMP-2 was significantly higher in the OLETF rats than in the LETO rats at 6 months of age, but not at 12. Conclusions The findings suggest that diabetes is associated with premature, excessive apoptosis of NP notochordal cells. This results in an accelerated transition of a notochordal NP to a fibrocartilaginous NP, which leads to early intervertebral disc degeneration. It remains to be determined if these premature changes are due to hyperglycemia or some other factors associated with diabetes. Understanding the mechanism by which diabetes affects disc degeneration is the first step in designing therapeutic modalities to delay or prevent disc degeneration caused by diabetes mellitus.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1054
Author(s):  
Wen-Cheng Lo ◽  
Chun-Chao Chang ◽  
Chun-Hao Chan ◽  
Abhinay Kumar Singh ◽  
Yue-Hua Deng ◽  
...  

Complications of diabetes mellitus (DM) range from acute to chronic conditions, leading to multiorgan disorders such as nephropathy, retinopathy, and neuropathy. However, little is known about the influence of DM on intervertebral disc degeneration (IVDD). Moreover, traditional surgical outcomes in DM patients have been found poor, and to date, no definitive alternative treatment exists for DM-induced IVDD. Recently, among various novel approaches in regenerative medicine, the concentrated platelet-derived biomaterials (PDB), which is comprised of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), etc., have been reported as safe, biocompatible, and efficacious alternatives for various disorders. Therefore, we initially investigated the correlations between DM and IVDD, through establishing in vitro and in vivo DM models, and further evaluated the therapeutic effects of PDB in this comorbid pathology. In vitro model was established by culturing immortalized human nucleus pulposus cells (ihNPs) in high-glucose medium, whereas in vivo DM model was developed by administering streptozotocin, nicotinamide and high-fat diet to the mice. Our results revealed that DM deteriorates both ihNPs and IVD tissues, by elevating reactive oxygen species (ROS)-induced oxidative stress, inhibiting chondrogenic markers and disc height. Contrarily, PDB ameliorated IVDD by restoring cellular growth, chondrogenic markers and disc height, possibly through suppressing ROS levels. These data imply that PDB may serve as a potential chondroprotective and chondroregenerative candidate for DM-induced IVDD.


2016 ◽  
Vol 25 (9) ◽  
pp. 2716-2720 ◽  
Author(s):  
Stella Maris Fabiane ◽  
Kirsten J. Ward ◽  
James C. Iatridis ◽  
Frances M. K. Williams

Aging Cell ◽  
2020 ◽  
Vol 19 (3) ◽  
Author(s):  
Dasheng Lin ◽  
Paolo Alberton ◽  
Manuel Delgado Caceres ◽  
Carina Prein ◽  
Hauke Clausen‐Schaumann ◽  
...  

Spine ◽  
2005 ◽  
Vol 30 (24) ◽  
pp. 2735-2742 ◽  
Author(s):  
Jeffrey J. T. Jim ◽  
Noora Noponen-Hietala ◽  
Kenneth M. C. Cheung ◽  
Jürg Ott ◽  
Jaro Karppinen ◽  
...  

Author(s):  
Saeeda Baig

During the recent past focus has shifted from identifying intervertebral disc degeneration as being caused by physical exposure and strain to being linked with a variety of genetic variations. The objective of this review is to provide an up to date review of the existing research data regarding the relation of intervertebral disc degeneration to structural protein genes and their polymorphisms and thus help clearly establish further avenues where research into causation and treatment is needed. A comprehensive search using the keywords “Collagen”, “COL”, “Aggrecan”, “AGC”, “IVDD”, “intervertebral disc degeneration”, and “lumbar disc degeneration” from PubMed and Google Scholar, where literature in the English language was selected spanning from 1991 to 2019. There are many genes involved in the production of structural components of an intervertebral disc. The issues in production of these components involve the over-expression or under-expression of their genes, and single nucleotide polymorphisms and variable number of tandem repeats affecting their structures. These structural genes include primarily the collagen and the aggrecan genes. While genetic and environmental factors all come into play with a disease process like disc degeneration, the bulk of research now shows the significantly larger impact of hereditary over exposure. While further research is needed into some of the lesser studied genes linked to IVDD and also the racial variations in genetic makeup, the focus in the near future should be on establishment of genetic testing to identify individuals at greater risk of disease and deliberation regarding the use of gene therapy to prevent disc degeneration.


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