Matrix Metalloproteinase-7 Degradation of Fetuin Blocks Fetuin-mediated Inhibition of Mineralization

Mechanisms underlying the association between atherosclerosis and periodontitis are not defined. Matrix metalloproteinases (MMPs) are increased in untreated periodontitis. Fetuin, a serum protein, inhibits vascular mineralization in humans. I hypothesized that MMP-7 affects fetuin function. In vitro mineralization was conducted based on methods developed by Hunter and colleagues. Mineralization was quantified using absorbance measurements (at 540 nm) of alizarin red bound to nascent crystals. Mineralization assays included intact MMP-3 and MMP-7-treated human and bovine fetuin (0-2 μM).The inhibition of mineralization mediated by fetuin (2 μM) was maximal at 3.5-4 hours. Transmission electron microscopy and electron diffraction analysis of crystals formed revealed the presence of hydroxyapatite. SDS-PAGE demonstrated that MMP-7 is more effective in digesting fetuin than MMP-3. The inhibitory effect of fetuin on mineralization was more reduced by MMP-7 digestion compared to MMP-3. Fetuin inhibits mineralization in vitro and this effect is reduced by MMP-7 degradation.MAS