Biomechanical properties and gene expression profiles of human cervical intervertebral discs in vitro
Fisher, Geoffrey D.
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The intervertebral disc is an integral component of the vertebral column. With its close proximity to the spinal cord and with functions that include load transmission, shock absorption, and neck motion, it is no surprise that complications involving the disc can often have serious ramifications. While the participation of both mechanical and molecular factors in disc function and pathology has been well-documented, no study in the current literature has determined if a correlation exists between disc mechanical properties and gene expression data. Twelve cadaveric cervical motion segments (C6-C7) were tested in unconfined axial compression in a 0.15 M saline solution at a rate of 0.1 mm/s. Samples of tissue from a separate disc (C7-T1) were subjected to gene expression profiling for 84 different genetic products via real time RT-PCR. Compressive modulus, failure strain, failure strength, strain energy density, and stress relaxation and hysteresis measures were calculated and tested for significant correlations against the steady-state mRNA levels of each target gene. Results showed significant positive correlations (|r|>0.576) of compressive modulus with the steady-state mRNA level of 23 different target genes including several collagens, integrins, laminins, and catenins. Failure strength, stress relaxation, and hysteresis also demonstrated significant correlations (all positive) with mRNA level for 2 genes each. These results suggest that compressive modulus plays an important role in the regulation of cervical disc gene expression. The positive correlations indicate that those discs routinely experiencing larger loads respond by increasing their transcription of certain genes, some of which are involved in cellular mechanotransduction. These findings identify several genes that might serve as future targets in improving clinical outcomes of cervical disc pathologies.