Collagen crosslinks in human lumbar intervertebral disc aging.
METHODS
Human lumbar intervertebral discs from individuals of varying ages were obtained at autopsy and analyzed for collagen crosslinks.


OBJECTIVE
To analyze alterations in collagen crosslinks in human lumbar intervertebral discs with aging and disc degeneration. Crosslinks studied were pyridinoline, which is a collagen maturation crosslink, and pentosidine, a nonenzymatically initiated age-related crosslink.


BACKGROUND
Crosslinking of collagen fibers within the matrix affects intervertebral disc biomechanics. In various connective tissues, alterations in pyridinoline and pentosidine crosslinks have been shown to predispose the tissue to mechanical failure. Little is known about the fate of intervertebral disc collagen crosslinks with advancing age and disc degeneration.


METHODS
Forty-two postmortem lumbar intervertebral discs were harvested from nine individuals whose ages were 24, 44, 47, 52, 67, 72, 75, 82, and 89 years. Degree of disc degeneration was graded macroscopically. Each lumbar disc was extracted with 4 mol/L guanidine hydrochloride, and the residual collagen was acid hydrolyzed and analyzed by reverse-phase high-performance liquid chromatography for pyridinoline and pentosidine crosslinks.


RESULTS
The findings indicate a decrease in pyridinoline and an increase in pentosidine crosslink levels with disc aging. The decrease in pyridinoline crosslinks with disc aging is a novel finding and may have detrimental effects on matrix resilience. Increased pentosidine levels have been implicated in the age-related deterioration of connective tissue. With advancing degrees of macroscopic disc degeneration, pentosidine levels increase, and pyridinoline levels are diminished.


CONCLUSIONS
Alterations in concentrations of pyridinoline and pentosidine collagen crosslinks occur with intervertebral disc aging and degeneration. These changes may contribute to the loss of disc integrity and play a role in the pathogenesis of the degenerative process.
Section of Orthopaedic Surgery, University of Chicago Spine Center, Illinois, USA. hpokham@surgery.bsd.uchicago.edu
H K
HK
Pokharna
F M
FM
Phillips
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000596:Amino Acids / Q000737:chemistry; D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry; D002102:Cadaver; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000209:etiology; D008159:Lumbar Vertebrae / Q000737:chemistry* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D008875:Middle Aged
D000596:Amino Acids; D003432:Cross-Linking Reagents; C015484:pyridinoline; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008239:Lysine