Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during intervertebral disc degeneration.

STUDY DESIGN: This study correlates the mRNA and protein levels of large and small proteoglycans with the morphologic grade of degeneration.

OBJECTIVES: To investigate changes in mRNA and protein levels of aggrecan, versican, biglycan, decorin and fibromodulin in the anulus fibrosus and the nucleus pulposus at different stages of tissue degeneration.

SUMMARY OF BACKGROUND DATA: Proteoglycans are found in both the anulus fibrosus and nucleus pulposus and contribute to the hydration of the tissue (aggrecan) and the regulation of matrix assembly (small proteoglycans). Changes in their abundance may influence the biochemical and biomechanical properties of the disc and may have an effect on disc function.

METHODS: Thirty-four human lumbar intervertebral discs were graded using Thompson's morphologic scale. The mRNA and protein content of aggrecan, versican, biglycan, decorin and fibromodulin was measured in extracts of anulus fibrosus and nucleus pulposus tissues dissected from these specimens. Protein levels were analyzed by Western blotting, and mRNA levels were semiquantified by reverse transcription polymerase chain reaction.

RESULTS: In the anulus fibrosus, the mRNA and protein content of all proteoglycans was significantly elevated at early stages of degeneration then declined in severely degenerated tissues. In contrast, matrix components in the nucleus pulposus showed a continuous decrease in content with increasing grade of degeneration.

CONCLUSIONS: Cells of the anulus fibrosus and nucleus pulposus react to tissue degeneration differently. Decreased mRNA expression by nucleus pulposus cells and declining protein content of the matrix make the nucleus more vulnerable to degeneration than the anulus. The cells in the anulus fibrosus respond to early degeneration by upregulating biosynthetic processes. However, in heavily degenerated tissues, the decline in the synthesis of aggrecan and the increase in the concentrations of small proteoglycans may be responsible for the failure of the repair processes.