Increased Matrix Metalloproteinase-2 and Bone Sialoprotein Response to Human Coronal Caries

Abstract

Background: It has been suggested that host matrix metalloproteinase-2 (MMP-2) present in dentin may be involved in caries progression, however, its response to caries is not known. Bone sialoprotein (BSP) has been implicated in dentin mineralization and MMP-2 modulation. Objective: To identify and compare the distribution of MMP-2 and BSP in healthy human coronal dentin and those with early caries. Methods: Freshly extracted 3rd molars and premolars with and without early caries were fixed, demineralized and subjected to immunohistochemistry using a monoclonal anti-MMP-2 antibody and monoclonal anti-BSP antibody with an avidin-biotin complex method. Immunoreactivity was visualized with 3,3′-diaminobenzidine substrate and observed under light microscopy. Results: Immunohistochemical analysis revealed that MMP-2 and BSP are not detected in the tubule lumens of healthy dentin. However, intense immunoreactivity for MMP-2 and BSP was detected in association with the full length of the caries-affected dentinal tubules. The MMP-2 and BSP at the dentino-enamel junction appeared unaltered. Conclusion: The results indicate that MMP-2 and BSP may be actively secreted by odontoblasts in response to carious insult. MMP-2 and BSP accumulation in the caries-affected dentinal tubules may indicate their potential involvement in the host defense mechanism which results in calcification of regions affected by the carious process.

Bone Sialoprotein, Matrix Metalloproteinases and Type I Collagen Expression after Sealing Infected Caries Dentin in Primary Teeth

“…Although the expression of MMP-2 and MMP-9 was not statistically different between the baseline and 60-day sample, we cannot rule out the fact that their expression was still high compared to that of sound teeth. This hypothesis can be reinforced by the observation that immunoreactivity for these MMPs in sound dentin was only shown to be present in predentin and the enamel-dentin junction [Boushell et al, 2011], but not around dentin tubules as detected in this study.…”

“…The evident labeling of MMP-2 surrounding dentin tubules may be related to MMP-2 newly secreted by odontoblasts as a reparative reaction, a finding already demonstrated in early studies of dentin caries [Toledano et al, 2010;Boushell et al, 2011]. Thus, the weak detection of MMP-2 in the intertubular dentin may be due to the short evaluation period after cavity sealing, which was probably not enough to allow diffusion of the newly secreted MMP-2 to the intertubular dentin.…”

“…In demineralized dentin, the literature has suggested that remnant intrafibrillar mineral crystallites that are present within the collagen might act as sites for apatite nucleation and re-growth [Bertassoni et al, 2011]. BSP provides the connection between collagen and the inorganic phase of dentin due to its high affinity for calcium and hydroxyapatite [Charadram et al, 2012] and has been identified around dentin tubules from caries dentin [Boushell et al, 2011]. In fact, the higher expression of BSP after cavity sealing, particularly around dentin tubules, may be considered as evidence of the remineralization process to which the carious dentin is susceptible after sealing.…”

Role of Dentin MMPs in Caries Progression and Bond Stability

“…Caries stimulates MMP-2 expression in human odontoblasts in vivo (Charadram et al 2012). MMP-2 seems to be actively secreted by odontoblasts in response to carious insult (Boushell et al 2011), resulting in the differential expression of this protease in sound, caries-affected, and caries-infected dentin (Toledano et al 2010;Charadram et al 2012). Increased levels of MMP-9 (Zehnder et al 2011) and MMP-20 (Sulkala et al 2002) in dentinal tubules under caries lesions have also been demonstrated.…”

“…More recently, MMPs were identified as being responsible for that activity (Tjäderhane et al 1998), and to date, the presence of gelatinases MMP-2 and -9 ( Fig. 1), collagenase MMP-8, stromelysin MMP-3, and MMP-20 have been reported (Martin-De Las Heras et al 2000;Sulkala et al 2002;Mazzoni et al 2007;Sulkala et al 2007;Boukpessi et al 2008;Mazzoni et al 2009;Santos et al 2009;Boushell et al 2011;.…”