Changes with age in proteoglycan synthesis in cells cultured in vitro from the inner and outer rabbit annulus fibrosus. Responses to interleukin-1 and interleukin-1 receptor antagonist protein.
METHODS
Proteoglycan synthesis was examined in cells isolated from the inner and outer annulus fibrosus of young and old rabbits. Their responses to interleukin-1 alpha and interleukin-1 receptor antagonist protein were investigated.


OBJECTIVE
To evaluate the age-related changes and the anatomically related differences in the function of intervertebral disc cells.


BACKGROUND
Proteoglycan content in the human intervertebral disc decreases with age. Age-related changes in intervertebral disc cell function, however, have not been fully investigated.


METHODS
Japanese white rabbits aged 2 months (young group) and 3 years (old group) were used. The inner and outer layer of the annulus fibrosus were separated. The proteoglycan synthesis and release were measured in cells cultured with or without human recombinant interleukin-1 alpha and interleukin-1 receptor antagonist protein.


RESULTS
The proteoglycan synthesis significantly decreased and the release rate significantly increased in the old rabbits, compared with the young ones. In the inner annulus, the inhibition of proteoglycan synthesis due to interleukin-1 alpha was greater in the old rabbits than in the young ones. In the old rabbits, interleukin-1-induced inhibition was more pronounced in the inner annulus than in the outer annulus. Interleukin-1 receptor antagonist protein suppressed inhibition of proteoglycan synthesis by interleukin-1 alpha in the two layers in both age groups.


CONCLUSIONS
Both the decline in proteoglycan synthesis and the increased cell sensitivity to interleukin-1 alpha with age may contribute to the degradation of discs. The increase in cell response to interleukin-1 alpha in the inner annulus of rabbits may explain why the inner annulus and nucleus pulposus degrade earlier than the outer annulus in human discs. Interleukin-1 receptor antagonist protein could be useful in inhibiting the degradation of the disc.
Maeda
S
S
Department of Orthopaedic Surgery, Tohoku University, School of Medicine, Sendai, Japan. s-maeda@mail.cc.tohoku.ac.jp
Kokubun
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S
D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis / Q000187:drug effects*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000494:pharmacology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011509:Proteoglycans; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins