MMP expression by intervertebral disc cells is responsive to changes in extracellular osmolarity

Abstract

We examined the response of cells from the central regions of the intervertebral disc, the nucleus pulposus (NP) to changes in extracellular osmolarity with particular reference to matrix metalloproteinases (MMPs) expression.NP cells were extracted from adult bovine caudal discs by enzyme digestion and cultured in alginate beads to maintain phenotype. MMP production was investigated by zymography and Western blotting, and total RNA was extracted from the cells and gene expression analysed using the Affymetrix GeneChip Bovine Genome Array.MMP‐2, MMP‐3 and MMP‐13 were significantly upregulated when cells were cultured in hypo‐osmotic medium i.e. 260 mOsm seen in severely degenerate discs compared to 356 and 489 mOsm seen in healthy discs. A similar upregulation was seen at the gene level.Our results show that expression of MMPs by disc cells is regulated by extracellular osmolarity, with MMP expression rising as osmolarity falls. These results could explain in part the findings that MMP expression increases with degree of disc degeneration i.e. with loss of aggrecan and fall in extracellular osmolarity.Grant Funding Source : AAA