Protein S100-A7 Derived from Digested Dentin Is a Critical Molecule for Dentin Pulp Regeneration

Komichi, Shungo; Takahashi, Yusuke; Okamoto, Masakazu; Ali, Muslim; Watanabe, Masakatsu; Huang, Haozhang; Nakai, Tadashi; Cooper, Paul R.; Hayashi, Mikako

doi:10.3390/cells8091002

Cited by 17 publications

(14 citation statements)

References 60 publications

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“…A heat map of the key transcripts for the osteo/dentinogenic differentiation process is shown in Figure 6E. These genes were consistent with those related to osteo/dentinogenic differentiation that were identified in previous reports [22][23][24][25][26][27][28][29][30][31][32][33].…”

Section: Rna Sequence Analysissupporting

confidence: 87%

Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair

et al. 2020

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Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biological molecules are effective in developing pulp capping materials based on wound healing by the dentin-pulp complex. Our group developed biodegradable viscoelastic polymer materials for tissue-engineered medical devices. The polymer contents help overcome the poor fracture toughness of hydroxyapatite (HAp)-facilitated osteogenic differentiation of pulp cells. However, the composition of this novel polymer remained unclear. This study evaluated a novel polymer composite, P(CL-co-DLLA) and HAp, as a direct pulp capping carrier for biological molecules. The biocompatibility of the novel polymer composite was evaluated by determining the cytotoxicity and proliferation of human dental stem cells in vitro. The novel polymer composite with BMP-2, which reportedly induced tertiary dentin, was tested as a direct pulp capping material in a rat model. Cytotoxicity and proliferation assays revealed that the biocompatibility of the novel polymer composite was similar to that of the control. The novel polymer composite with BMP-2-induced tertiary dentin, similar to hydraulic calcium-silicate cement, in the direct pulp capping model. The BMP-2 composite upregulated wound healing-related gene expression compared to the novel polymer composite alone. Therefore, we suggest that novel polymer composites could be effective carriers for pulp capping.

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Section: Rna Sequence Analysissupporting

confidence: 87%

Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair

et al. 2020

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“…dECM biomaterials undergo proteolytic digestion once implanted and several studies have shown that chemical or enzymatic breakdown of dECM biomaterials produces novel or hidden cryptic ECM molecules and can modify the biological properties of dECMs [ 46 – 49 ], including the recruitment of MSCs [ 40 ]. For example, protein S100-A7 derived from MMP-20 digested dentin matrix was shown to recruit CD146 positive cells to the site of wounded dental pulp in a rat model [ 50 ]. A collagen III-derived peptide isolated from a dECM by proteolytic degradation was shown to be chemotactic towards human cortical neural stem cells, adipocyte stem cells, myoblast cells and Schwann cells in vitro and in vivo [ 45 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

A novel chemotactic factor derived from the extracellular matrix protein decorin recruits mesenchymal stromal cells in vitro and in vivo

et al. 2020

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Soft tissue is composed of cells surrounded by an extracellular matrix that is made up of a diverse array of intricately organized proteins. These distinct components work in concert to maintain homeostasis and respond to tissue damage. During tissue repair, extracellular matrix proteins and their degradation products are known to influence physiological processes such as angiogenesis and inflammation. In this study we developed a discovery platform using a decellularized extracellular matrix biomaterial to identify new chemotrophic factors derived from the extracellular matrix. An in vitro culture of RAW.264 macrophage cells with the biomaterial ovine forestomach matrix led to the identification of a novel~12 kDa chemotactic factor, termed 'MayDay', derived from the N-terminal 31-188 sequence of decorin. The recombinant MayDay protein was shown to be a chemotactic agent for mesenchymal stromal cells in vitro and in vivo. We hypothesize that the macrophage-induced cleavage of decorin, via MMP-12, leads to the release of the chemotactic molecule MayDay, that in turn recruits cells to the site of damaged tissue.

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“…We previously reported that matrix metalloproteinase-20 digested organic dentin matrix components (DMCs) promoted tertiary dentin formation ( Okamoto et al 2018 ). Moreover, proteome analysis of the digested DMCs revealed that protein S100A7 (S100A7) and S100A8 promoted pulpal wound healing ( McLachlan et al 2004 ; Komichi et al 2019 ). S100A7 and S100A8 are both present in dentin and pulp; they promoted tertiary dentin formation in a rat DPC model ( Komichi et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Functional Peptide for Next-Generation Vital Pulp Therapy

et al. 2022

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Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography–tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

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Protein S100-A7 Derived from Digested Dentin Is a Critical Molecule for Dentin Pulp Regeneration

Cited by 17 publications

References 60 publications

Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair

Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair

A novel chemotactic factor derived from the extracellular matrix protein decorin recruits mesenchymal stromal cells in vitro and in vivo

Novel Functional Peptide for Next-Generation Vital Pulp Therapy

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