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MOLECULAR AND IMMUNOHISTOLOGIC ASPECTS OF DISC DEGENERATION: AN IN VIVO ANIMAL STUDY



Abstract

Study Design: Experimental in vivo study on New Zealand White Rabbits.

Summary of Background Data: We have developed an in-vivo rabbit model of lumbar disc degeneration. This model provides a defined loading of one single disc. However, the molecular mechanism that leads to mechanically-induced disc degeneration remains unclear.

Objective: To investigate the process of mechanically induced disc degeneration in New Zealand White Rabbits with respect to remodeling on the gene and the level of protein expression.

Subjects: Seven animals were treated with an external compression-device applying 200N on segment L3/4. Eight animals underwent sham surgery.

Outcome Measures: After 28 days discs were harvested and cut into two pieces in a sagittal plain. One piece was used for protein analysis utilizing immunohistochemical protocols for collagen I, II and aggrecan. The other half of the disc was used for quantitative real-time RT-PCR to determine gene expression of selected matrix genes.

Results: In the compression group matrix genes were upregulated: collagen I (6.46x; p=0,018), collagen II (2.14x), biglycan (2.97x; p=0,049), decorin (4.64x; p=0,043), aggrecan (1.2x), osteonectin (2.03x), fibronectin (3.48x), fibromodulin (2.6x; p=0,037). The MMP-13 gene could only be detected in compressed discs. Gene transcripts of the metalloproteinase-inhibitor TIMP-1 were 4.5 times upregulated (p=0,007). Immunohistochemical analysis revealed a decrease of aggrecan and collagen I.

Conclusions: In our animal model mechanical loading caused degradation of the matrix proteins collagen I and aggrecan. Metalloproteinases like MMP-13 trigger this degenerative process. The elevated expression of matrix genes and TIMP-1 transcripts may characterize a mechanism of compensation.

These abstracts were prepared by Mr. Brian J C Freeman FRCS (Tr & Orth). Correspondence should be addressed to him at The Centre for Spinal Studies and Surgery, University Hospital, Queens Medical Centre, Nottingham NG7 2UH.