The expression of anabolic cytokines in intervertebral discs in age-related degeneration.
METHODS
Quantitative analysis of endogenous messenger ribonucleic acid (mRNA) expression of anabolic cytokines in the anulus fibrosus and nucleus pulposus tissue from the intervertebral discs of young and old rabbits was performed.


OBJECTIVE
To measure the expression of anabolic cytokines bone morphogenetic protein-2 (BMP-2), BMP-7, transforming growth factor-beta (TGF-beta), and insulin-like growth factor-I (IGF-I) in the anulus fibrosus and nucleus pulposus tissue from young and old rabbits to determine if there are differences with age.


BACKGROUND
Disc degeneration increases with age and is associated with compromised disc chondrocytic function. Molecules such as BMP-2, BMP-7, TGF-beta, and IGF-I are known to up-regulate disc cell synthesis of key chondrocytic matrix molecules in vitro, and have been proposed as therapeutic agents to prevent disc degeneration. Previous studies have shown that exogenous anabolic cytokines can up-regulate disc-cell function both in vitro and in vivo, however, the endogenous expression of anabolic cytokines in the disc is still unknown.


METHODS
New Zealand white rabbits aged 3 years (old) and 6 months (young) were used. Quantitative real-time polymerase chain reaction was performed to measure the mRNA levels of BMP-2, BMP-7, TGF-beta1, and IGF-I from anulus fibrosus and nucleus pulposus tissue from young and old rabbits. The discs form the young rabbits represent nondegenerated discs, and the discs from the old rabbits represent discs at the onset of degeneration.


RESULTS
In the nucleus pulposus, the mRNA levels, given as a ratio of old to young, were 3.6 for BMP-2 (P = 0.004), 61 for BMP-7 (P = 0.02), 4.0 for TGF-beta1 (P = 0.3), and 0.6 for IGF-I (P = 0.2). In the anulus fibrosus, the mRNA levels, given as a ratio of old to young, were 1.6 for BMP-2 (P = 0.07), 4.6 for BMP-7 (P = 0.004), 2.9 for TGF- beta1 (P = 0.01), and 2.0 for IGF-I (P = 0.1).


CONCLUSIONS
The disc tissue from the old rabbits as compared to the young rabbits showed, in general, significantly higher mRNA levels of endogenous BMP-2, BMP-7, and TGF-beta in both the anulus fibrosus and nucleus pulposus. The similar patterns of up-regulation in gene expression with age shown by these 3 anabolic cytokines suggest a common pathway in terms of regulation and transcription in the early stage of disc degeneration. The knowledge of the age-related pattern in endogenous gene expression of these anabolic cytokines could provide important information for clinical interventional therapy.
Murakami
Hideki
H
Department of Orthopaedic Surgery, Iwate Medical University School of Medicine, Morioka, Japan.
Yoon
S Tim
ST
Attallah-Wasif
Emad S
ES
Tsai
Kai-Jow
KJ
Fei
Qinming
Q
Hutton
William C
WC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013122:Spinal Diseases / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I