期刊
JOURNAL OF ORTHOPAEDIC RESEARCH
卷 33, 期 5, 页码 738-746出版社
WILEY
DOI: 10.1002/jor.22807
关键词
intervertebral disc degeneration; type 2 diabetes; vertebral endplate; advanced glycation end-products; pentosidine
类别
资金
- North American Spine Society
- National Institutes of HealthAR063705
- Orthopaedic Research and Education Foundation
- UCSF Diabetes and Endocrinology Research Center
- NIH [S10RR026645, AT002993, DK-087307, DK-095980]
- Department of Preventive and Restorative Dental Sciences at UCSF
- Department of Orofacial Sciences at UCSF
- UC Office of the President
Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 +/- 7days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end-product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia-inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE-mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:738-746, 2015.
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