Immuno morphological Analysis of RAGE Receptor Expression and NF-κB Activation in Tissue Samples from Normal and Degenerated Intervertebral Discs of Various Ages

摘要

We immunohistochemically investigated the pattern of RAGE expression and NFκB translocation into the nucleus in 43 com plete cross-sections of human lumbar intervertebral discs (neonatal— 85 years) and compared this with the carboxymethyl-lysine (CML) mod ification of proteins as a marker for oxidative stress. No significant ex pression of RAGE, no obvious activation of NF-kB, and no deposition of CML-modified proteins were seen in fetal, juvenile, and young adoles cent discs (until age of 13 years). In adults, 25-50% of nucleus pulposus cells were labeled for RAGE and activated NF-κB, which correlated well with the occurrence and extent of CML staining in the pericellular ma trix. In the annulus fibrosus significantly lower values were seen than in the nucleus pulposus. In consequence, we provide evidence for activa tion of the NF-κB system in intervertebral discs in vivo, which correlates with accumulated oxidative stress and increases in age and disc degener ation. Oxidative stress (as monitored by CML modifications) may lead to RAGE activation and NF-κB translocation.