The C‐terminus of the amelogenin peptide influences the proliferation of human bone marrow mesenchymal stem cells

Kunimatsu, Ryo; Awada, Tetsuya; Yoshimi, Yuki; Ando, Kazuyo; Hirose, Naoto; Tanne, Yuki; Sumi, Keisuke; Tanimoto, Kotaro

doi:10.1002/jper.17-0087

Cited by 7 publications

(7 citation statements)

References 49 publications

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“…Amelogenins are crucial components of developing extracellular enamel matrix, which direct the organization and mineralization of enamel. Studies have demonstrated that C-terminus of amelogenins induces division, differentiation, and maturation of MSCs, especially in cementoblastic lineage cells (Kunimatsu et al, 2017(Kunimatsu et al, , 2018. Additionally, cementoblastic differentiation of mesenchymal progenitor cells is tightly maintained by an autocrine system mediated by parathyroid hormone (PTH)related peptide (PTHrP) and the PTH/PTHrP receptor, thereby preventing DMSCs from premature differentiation into cementoblasts (Takahashi et al, 2019).…”

Section: Cementogenesismentioning

confidence: 99%

Dental-Derived Mesenchymal Stem Cells: State of the Art

Ouchi

Cao

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs’ functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.

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Section: Cementogenesismentioning

confidence: 99%

Dental-Derived Mesenchymal Stem Cells: State of the Art

Ouchi

Cao

et al. 2021

Front. Cell Dev. Biol.

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“…The selection sequence consisted of the evaluation of the title (2873 articles), of the abstract (774 articles), and subsequently of the complete text (24 articles) (Figure 1). Of the latter, 10 [24][25][26][27][28][29][30][31][32][33] were excluded due to the descriptive analysis (Table 1), while 14 studies met the inclusion criteria (Table 2). In the 14 studies selected [8,[34][35][36][37][38][39][40][41][42][43][44][45][46], it was not possible to perform a quantitative analysis due to major differences in terms of the cell model, peptide concentrations, time points, and methodologies employed (Table 2).…”

Section: Systematic Reviewmentioning

confidence: 99%

Amelogenin-Derived Peptides in Bone Regeneration: A Systematic Review

Fiorino

Marturano

Placella

et al. 2021

IJMS

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Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived peptides, named LRAP, TRAP, SP, and C11, in bone tissue engineering. Interestingly, these peptides seem to maintain or even improve the biological activity of the full-length protein, which has received attention in the field of bone regeneration. In this article, the authors combined a systematic and a narrative review. The former is focused on the existing scientific evidence on LRAP, TRAP, SP, and C11’s ability to induce the production of mineralized extracellular matrix, while the latter is concentrated on the structure and function of amelogenin and amelogenin-derived peptides. Overall, the collected data suggest that LRAP and SP are able to induce stromal stem cell differentiation towards osteoblastic phenotypes; specifically, SP seems to be more reliable in bone regenerative approaches due to its osteoinduction and the absence of immunogenicity. However, even if some evidence is convincing, the limited number of studies and the scarcity of in vivo studies force us to wait for further investigations before drawing a solid final statement on the real potential of amelogenin-derived peptides in bone tissue engineering.

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“…A recent in vitro study suggested that bone marrow MSC proliferation was increased in the presence of C-terminal of amelogenin and inhibited by anti-LAMP1 antibody or U0126. Increased phosphorylated ERK1/2 was observed in the presence of C-terminal of amelogenin, and decreased phosphorylated ERK1/2 was seen in the presence of anti-LAMP1 antibody or U0126 [39]. Recently it has been demonstrated that human recombinant amelogenin remarkably enhanced LAMP-1 staining in mouse cementblasts [40].…”

Section: Discussionmentioning

confidence: 98%

Effects of human full-length amelogenin on the proliferation of human osteoblasts

Kunimatsu¹,

Yoshimi²,

Awada³

et al. 2018

biomedicalresearch

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Objective: Amelogenins are known as a major constituent of the enamel matrix secreted by ameloblasts and play an important role in enamel formation. Amelogenin knockout mice exhibit enhanced osteoblast formation and resorption of tooth cementum. Recent studies have revealed that amelogenins also have cell signaling properties. However, the biological functions of amelogenin in osteoblasts remain unclear. In this study, we examined the effects of recombinant human full-length amelogenin (rh174) on the proliferation of cultured normal human osteoblasts (NHOst). Methods: NHOst cells were cultured and treated with 100 ng/ml rh174. Cell proliferation was evaluated using MTS assay in a time-dependent manner. Expression of Lysosomal-associated membrane protein 1 (LAMP 1), a possible amelogenin receptor, in NHOst cells was analyzed. NHOst cells were cultured and treated with 100 ng/ml rh174 in the presence or absence of LAMP 1-blocking antibody. Cell proliferative activity was analyzed by BrdU assay. Phosphorylation of extracellular signal regulated kinases (ERK) 1/2 was measured by ELISA and western blotting analysis. Results: Proliferation of NHOst cells was enhanced significantly (p<0.01) by treatment with rh174, and was inhibited significantly (p<0.01) by addition of anti-LAMP 1-blocking antibody. In addition, the ratio of phosphorylated ERK1/2 to total ERK1/2 was significantly larger (p<0.01) with rh174 treatment, and was reduced significantly by the addition of anti-LAMP 1-blocking antibody in NHOst cells. Conclusion: These results confirmed that rh174 interacts with LAMP 1, and rh174/LAMP 1 interaction activates the ERK1/2 signaling pathway, enhancing the proliferation activity of NHOst cells.

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The C‐terminus of the amelogenin peptide influences the proliferation of human bone marrow mesenchymal stem cells

Abstract: A C-terminal amelogenin variant increased the proliferation of MSCs via an interaction with LAMP1 and the MAPK-ERK signaling pathway, indicating the possibility of using MSCs for tissue regeneration in the craniofacial region.

Cited by 7 publications

References 49 publications

Dental-Derived Mesenchymal Stem Cells: State of the Art

Dental-Derived Mesenchymal Stem Cells: State of the Art

Amelogenin-Derived Peptides in Bone Regeneration: A Systematic Review

Effects of human full-length amelogenin on the proliferation of human osteoblasts

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