Study Design: Experimental in vivo study on New Zealand white rabbits.

Summary of Background Data: Bone Morphogenetic Protein 2 (BMP-2) is of increasing orthopaedic interest due to its osteo-inductive potency. Currently it is used in human and animal studies for posterolateral spinal fusions. However, little data is available concerning the pathophysiologic role of BMP-2 in normal and degenerated discs.

Methods: A recently established animal model was used to create mechanically induced disc degeneration of one single segment. In 6 animals, an external disc compression device was attached for 28 days. For comparison 8 animals underwent a sham operation.

Outcome Measures: The discs were analysed by a) immunohistology to determine protein content of BMP-2 and b) real time RT-PCR to quantify RNA content of BMP-2.

Results: Sham controls showed a homogeneous distribution of BMP-2 throughout the annulus fibrosus and cluster-like accumulation within the nucleus pulposus. Mechanically degenerated discs determined a reduction of positive cells with areas lacking BMP-2. Real time RT-PCR results demonstrated a statistically significant (7.92 times) upregulation of BMP-2 as compared with shams (p=0.033).

Conclusions: Mechanically induced disc degeneration is associated with a loss of BMP-2 protein. Disc cells respond with a stimulation of BMP-2 gene expression. This data confirms the role of BMP-2 in the pathophysiology of disc remodeling. It remains unclear if this mechanism of BMP-2 stimulation contributes to the disc reorganization alone or if it may also play a role in osteo-inductive processes like osteophyte formation or endplate sclerosis.

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.