The biological basis of degenerative disc disease: proteomic and biomechanical
analysis of the canine intervertebral disc
#MMPMID26341258
Erwin WM
; DeSouza L
; Funabashi M
; Kawchuk G
; Karim MZ
; Kim S
; M?dler S
; Matta A
; Wang X
; Mehrkens KA
Arthritis Res Ther
2015[Sep]; 17
(1
): 240
PMID26341258
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INTRODUCTION: In the present study, we sought to quantify and contrast the
secretome and biomechanical properties of the non-chondrodystrophic (NCD) and
chondrodystrophic (CD) canine intervertebral disc (IVD) nucleus pulposus (NP).
METHODS: We used iTRAQ proteomic methods to quantify the secretome of both CD and
NCD NP. Differential levels of proteins detected were further verified using
immunohistochemistry, Western blotting, and proteoglycan extraction in order to
evaluate the integrity of the small leucine-rich proteoglycans (SLRPs) decorin
and biglycan. Additionally, we used robotic biomechanical testing to evaluate the
biomechanical properties of spinal motion segments from both CD and NCD canines.
RESULTS: We detected differential levels of decorin, biglycan, and fibronectin,
as well as of other important extracellular matrix (ECM)-related proteins, such
as fibromodulin and HAPLN1 in the IVD NP obtained from CD canines compared with
NCD canines. The core proteins of the vital SLRPs decorin and biglycan were
fragmented in CD NP but were intact in the NP of the NCD animals. CD and NCD
vertebral motion segments demonstrated significant differences, with the CD
segments having less stiffness and a more varied range of motion. CONCLUSIONS:
The CD NP recapitulates key elements of human degenerative disc disease. Our data
suggest that at least some of the compromised biomechanical properties of the
degenerative disc arise from fibrocartilaginous metaplasia of the NP secondary to
fragmentation of SLRP core proteins and associated degenerative changes affecting
the ECM. This study demonstrates that the degenerative changes that naturally
occur within the CD NP make this animal a valuable animal model with which to
study IVD degeneration and potential biological therapeutics.
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