Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes

Aaron J. Fields, Britta Berg-Johansen, Lionel N. Metz, Stephanie Miller, Brandan La, Ellen C. Liebenberg, Dezba G. Coughlin, James L. Graham, Kimber Stanhope, Peter J Havel, Jeffrey C. Lotz

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)738-746
Number of pages9
JournalJournal of Orthopaedic Research
Volume33
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • advanced glycation end-products
  • intervertebral disc degeneration
  • pentosidine
  • type 2 diabetes
  • vertebral endplate

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes'. Together they form a unique fingerprint.

  • Cite this

    Fields, A. J., Berg-Johansen, B., Metz, L. N., Miller, S., La, B., Liebenberg, E. C., Coughlin, D. G., Graham, J. L., Stanhope, K., Havel, P. J., & Lotz, J. C. (2015). Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes. Journal of Orthopaedic Research, 33(5), 738-746. https://doi.org/10.1002/jor.22807