Immunohistochemical Localization of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the Forming Rat Incisor

Goldberg, Michel; Septier, D.; Bourd, Katia; Hall, Richard L.; George, Anne; Goldberg, Harvey A.; Ménashi, Suzanne

doi:10.1080/03008200390223927

Cited by 51 publications

(28 citation statements)

References 42 publications

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“…At the light microscope level, few studies have reported the distribution of these SLRPs during tooth development, although their distribution has been extensively examined using iEM. The patterns observed in the current light microscopy study resemble those demonstrated by Goldberg and co-workers [26] in the mouse first molar at post-natal day one. However, their study demonstrated significant levels of BGN, DCN and FMD in the developing enamel organ, which differs from the present study.…”

Section: Discussionsupporting

confidence: 88%

Osteoadherin Accumulates in the Predentin towards the Mineralization Front in the Developing Tooth

et al. 2012

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BackgroundProteoglycans (PG) are known to be involved in the organization and assembly of the extracellular matrix (ECM) prior to mineral deposition. Osteoadherin (OSAD), a keratan sulphate PG is a member of the small leucine-rich (SLRP) family of PGs and unlike other SLRPs, OSAD expression is restricted to mineralized tissues. It is proposed to have a high affinity for hydroxyapatite and has been shown to be expressed by mature osteoblasts but its exact role remains to be elucidated.Methodology/Principal FindingsWe investigated the protein distribution of OSAD in the developing mouse tooth using immunohistochemistry and compared its expression with other SLRPs, biglycan (BGN), decorin (DCN) and fibromodulin (FMD). OSAD was found to be specifically localized in the predentin layer of the tooth and focused at the mineralization front. These studies were confirmed at the ultrastructural level using electron microscopy (iEM), where the distribution of immunogold labeled OSAD particles were quantified and significant amounts were found in the predentin, forming a gradient towards the mineralization front. In addition, iEM results revealed OSAD to lie in close association with collagen fibers, further suggesting an important role for OSAD in the organization of the ECM. The expression profile of mineralization-related SLRP genes by rat dental pulp cells exposed to mineralization inducing factors, showed an increase in all SLRP genes. Indeed, OSAD expression was significantly increased during the mineralization process, specifically following, matrix maturation, and finally mineral deposition. Alizarin Red S staining for calcium deposition showed clear bone-like nodules, which support matrix maturation and mineralization.ConclusionsThese studies provide new evidence for the role of OSAD in the mineralization process and its specific localization in the predentin layer accumulating at the mineralization front highlighting its role in tooth development.

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Section: Discussionsupporting

confidence: 88%

Osteoadherin Accumulates in the Predentin towards the Mineralization Front in the Developing Tooth

et al. 2012

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“…Several MMPs have been identified in dentin and pulp (Boukpessi et al , 2008, Goldberg et al, 2003, Palosaari et al , 2003) and are thought to be implicated in the early stages of dentinogenesis. Among endogenous MMPs, MMP-2 has been proposed to be involved in dental ECM processing taking place at later stages of tooth development, and particularly in dentin sialophosphoprotein (DSPP) processing, possibly in association with MMP-20 (Bourd-Boittin et al , 2005, Yamakoshi et al , 2006), or in association with a self-processing mechanism of DSPP (Godovikova and Ritchie, 2007).…”

Section: Introductionmentioning

confidence: 99%

MMP2-cleavage of DMP1 generates a bioactive peptide promoting differentiation of dental pulp stem/progenitor cell

Chaussain

Eapen

Huet

et al. 2009

eCM

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Dentin Matrix Protein 1 (DMP1) plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2) is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain) domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N-and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP) and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury.

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“…Along with the presence of several proteinases in the enamel space to degrade EMPs3456, the transporting mechanisms of EMP debris across ameloblasts are of equal importance in ensuring enamel health. Earlier understanding of cellular uptake of EMPs from enamel space seems to favor a passive diffusion or non-specific internalization pattern1213141516.…”

Section: Discussionmentioning

confidence: 99%

“…Ameloblasts in secretory stage mainly function to synthesize and secrete a series of enamel matrix proteins (EMPs) into the future enamel space2. During enamel maturation, EMPs are fragmented extracellularly in the presence of ameloblast-derived proteinases3456. The EMP debris is retrieved by ameloblasts for further degradation within the cellular endosomal/lysosomal apparatus789, and the concomitant ion flux through the ameloblasts gives rise to mature tooth enamel with highly organized crystal structure.…”

mentioning

confidence: 99%

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

Yin

Lin

Guo

et al. 2017

Sci Rep

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Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

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Immunohistochemical Localization of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the Forming Rat Incisor

Cited by 51 publications

References 42 publications

Osteoadherin Accumulates in the Predentin towards the Mineralization Front in the Developing Tooth

Osteoadherin Accumulates in the Predentin towards the Mineralization Front in the Developing Tooth

MMP2-cleavage of DMP1 generates a bioactive peptide promoting differentiation of dental pulp stem/progenitor cell

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

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