Does Type II Diabetes Induce Early Senescence and Degeneration in Human Intervertebral Discs? A Tissue Biomarker Evaluation

Abstract

Background: Diabetes mellitus is one of the leading causes of morbidity resulting in multi-organ dysfunction. Animal studies have shown that hyperglycemia results in stress-induced senescence through the p16-pRb pathway, thereby accelerating early disc degeneration. There is a paucity of literature on the effect of hyperglycemia in human intervertebral disc cells. We aimed to analyze the effect of diabetes mellitus in human intervertebral disc cells. Methods: This is a prospective study done in patients with degenerative disc disease. Patients were categorized into a control group (no diabetes: 26 patients) and a study group (type 2 diabetes for. 3 years: 24 patients). All patients underwent either discectomy or transforaminal lumbar interbody fusion and the removed disc was transported to pathology department. Tissue was prepared and histopathological grading was done followed by immunohistochemistry studies using antibodies for MMP-1, p21, p16, and pRb. Results: Samples from diabetic patients had severe (grade 2) degenerative changes compared with the control group (grade 1). Changes were more intense in the nucleus pulposus with increased cellularity and clustering of chondrocytes, and disorganization and loss of nuclear matrix. Immunohistochemical staining for MMP1, p16, and pRb was more intense (Q score ¼ 4) whereas the staining for p21 was less intense (Q score ¼ 1) in the diabetic group compared with the control group. Conclusion: Our study demonstrates that type 2 diabetes mellitus accelerates stress-induced senescence in human intervertebral discs resulting in early disc degeneration. Also, the severity of disc degeneration is severe compared with the normal subjects. Clinical Relevance: Hyperglycemia can affect the intervertebral discs similar to other organs and hence adequate control of blood glucose in diabetics can prevent the disc degeneration, which is the initiator of degeneration cascade in spine.

Platelet-Derived Biomaterials Exert Chondroprotective and Chondroregenerative Effects on Diabetes Mellitus-Induced Intervertebral Disc Degeneration

“…During in vivo investigations, STZ + NA and HFD-induced DM mice showed structural malformation of IVD, in the terms of narrowed disc height and highly reduced levels of chondrogenic markers including SOX9, type 2 collagen and aggrecan at gene and protein levels, representing IVDD. These results are in line with a prospective study of 24 patients, T2DM hastened stress-induced deformed NP with clustered chondrocytes and enhanced cellularity, leading to IVD senescence and disc degeneration [31]. A retrospective study also concluded that prolonged T2DM and its bad control could result in severe disc degeneration [5].…”

Network Pharmacological Dissection of the Mechanisms of Eucommiae Cortex-Achyranthis Radix Combination for Intervertebral Disc Herniation Treatment

“…Cellular senescence of IVD cells is the most important pathophysiological mechanism underlying IVD degeneration leading to IDH, and the antisenescence-based pharmacological strategies may be effective in preventing or attenuating the disease onset and progression. [123][124][125][126][127][128][129][130][131][132][133][134] The chemokine pathway is an inflammatory pathomechanism associated with IDH development and its activity is related to the generation, persistence, and severity of neuropathic and radicular pain induced by IDH; additionally, targeting this pathway may hold therapeutic potential. 122,[135][136][137][138][139] The Fork head box O (FoxO) pathway has an antioxidant effect that can protect IVDs against their degeneration induced by oxidative stress.…”

Does Vitamin K2 Influence the Interplay between Diabetes Mellitus and Intervertebral Disc Degeneration in a Rat Model?

“…Mutations of the IL-10 gene were implicated in IVD degeneration [ 19 , 20 , 21 ]. Sudhir et al linked IVDD in diabetic patients to the production and accumulation of ROS, causing oxidative stress, DNA damage, cellular apoptosis, altered gene expressions and production of inflammatory cytokines, growth factors and degradative enzymes [ 22 ]. Heme oxygenase-1 (HMOX1) is implicated in protection against tissue injury [ 23 ].…”