title: Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes.
abstract: 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 ± 7 days). 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.
authors: Orthopaedic Bioengineering Laboratory, Department of Orthopaedic Surgery, University of California, San Francisco, California.
authors: Aaron J
authors: AJ
authors: Fields
authors: Britta
authors: B
authors: Berg-Johansen
authors: Lionel N
authors: LN
authors: Metz
authors: Stephanie
authors: S
authors: Miller
authors: Brandan
authors: B
authors: La
authors: Ellen C
authors: EC
authors: Liebenberg
authors: Dezba G
authors: DG
authors: Coughlin
authors: James L
authors: JL
authors: Graham
authors: Kimber L
authors: KL
authors: Stanhope
authors: Peter J
authors: PJ
authors: Havel
authors: Jeffrey C
authors: JC
authors: Lotz
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001857:Bone Matrix / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006706:Homeostasis; D007403:Intervertebral Disc / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012598:Sclerosis
chemical_list: D017127:Glycation End Products, Advanced; D006025:Glycosaminoglycans
keywords: advanced glycation end-products; intervertebral disc degeneration; pentosidine; type 2 diabetes; vertebral endplate
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