Dentonin, a Fragment of MEPE, Enhanced Dental Pulp Stem Cell Proliferation

Liu, H.; Li, W.; Gao, Canzhu; Kumagai, Yoshinari; Blacher, Russell; DenBesten, Pamela

doi:10.1177/154405910408300612

Cited by 66 publications

(56 citation statements)

References 23 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is reported that AC-100 enhances osteogenesis by promoting osteoblast proliferation and differentiation like BMP-2 (8,9). Dentonin, which is the same as AC-100, promotes dental pulp stem cell proliferation in response to the dentin repair response (34,35). Furthermore, Bmp-2, Dlx5, and Mepe expressions are increased during healing of a bone fracture (36).…”

Section: Mepe Expression Is Strongly Stimulated By Bmp-2 Treatment Anmentioning

confidence: 99%

Molecular Regulation of Matrix Extracellular Phosphoglycoprotein Expression by Bone Morphogenetic Protein-2

Cho¹,

Yoon²,

Woo³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Matrix extracellular phosphoglycoprotein (MEPE) is mainly expressed in mineralizing tissues, and its C-terminal proteolytic cleavage product is an acidic-serine-asparate-rich-MEPE-associated motif (ASARM) that is a strong regulator of body phosphate metabolism and mineralization. There is sufficient data supporting a role for MEPE protein function in mineralization, however, little is known about the regulation of MEPE gene expression. As bone morphogenetic protein-2 (BMP-2) is one of the most important signals for calvarial mineralization and MEPE expression is higher in mineralized tissues, we attempted to uncover a regulatory circuit between BMP-2 and MEPE expression. Mepe expression is very low in proliferating MC3T3-E1 cells, but is dramatically increased in the mineralization stage and is strongly stimulated by treatment with BMP-2, even in proliferating cells. Overexpression and knockdown experiments of Smads, Dlx5, and Runx2 indicated that they are indispensable mediators of BMP-2-induced Mepe expression. In contrast, Msx2 showed strong inhibition of Mepe transcription. PHEX is an enzyme that prevents the release of the ASARM motif, a mineralization inhibitor, from the MEPE molecule. Thus, the MEPE/PHEX ratio may be a good indicator of mineralization progression because we found that the mRNA ratio and protein levels were low when osteoblasts were actively differentiating to the mineralization stage and the ratio was high when the cells reached the mineralization stage when it is assumed that osteocytes may protect themselves and make a space to survive from the mineralized matrix by releasing the ASARM motif. Collectively, MEPE expression is bone cell-specific and induced by the BMP-2 signaling pathway. In addition, the MEPE/PHEX ratio of the cell could be a very important barometer indicating the progression of tissue mineralization.Mineral homeostasis in the body is critical for healthy bones and teeth, and is generally regulated by the calcium-phosphate balance in the bone and kidney networks. In the past, the vitamin D/parathyroid hormone axis was assumed to be a single major circuit in bone-renal phosphate regulation, but recently, new bone-renal phosphate regulating factors have been identified. The finding of fibroblast growth factor 23 (FGF23), 2 phosphate-regulating genes with homologies to endopeptidases on the X chromosome (PHEX) and matrix extracellular phosphoglycoprotein (MEPE) genes, and their pathophysiological roles in the genetic diseases of mineral metabolism, have provided a great deal of insight into the understanding of bone-and mineral-related diseases. Among these, autosomal-dominant hypophosphatemic rickets (OMIM number 193100) is characterized by renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D 3 levels (1). Autosomal-dominant hypophosphatemic rickets is caused by a missense mutation of FGF23, which is resistant to proteolysis by PHEX and increases the half-life of full-length phosphaturic FGF23 (2). Second, X-linked hypophosphatemic...

show abstract

Section: Mepe Expression Is Strongly Stimulated By Bmp-2 Treatment Anmentioning

confidence: 99%

Molecular Regulation of Matrix Extracellular Phosphoglycoprotein Expression by Bone Morphogenetic Protein-2

Cho¹,

Yoon²,

Woo³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Several phosphorylation sites are known, and a region containing a RGD and a SGDG motif has attracted attention in the search for a bioactive peptide. The end result is a 23 amino acid synthetic peptide containing these two motifs called AC-100, or more commonly dentonin [10,11]. Due to their respective interactions with integrins and glycosaminoglycans, RGD and SGDG motifs have two functions: (1) regulation of bone homeostasis by facilitating cell-matrix interactions and differentiation of osteoblasts; and (2) activation of cell proliferation [10].…”

Section: Introductionmentioning

confidence: 99%

“…Due to their respective interactions with integrins and glycosaminoglycans, RGD and SGDG motifs have two functions: (1) regulation of bone homeostasis by facilitating cell-matrix interactions and differentiation of osteoblasts; and (2) activation of cell proliferation [10]. Dentonin was successfully used to activate osteogenesis in vitro and in vivo [10], and to stimulate dental pulp stem cell proliferation in order to repair dentin damages in rodents [11,12].…”

Section: Introductionmentioning

confidence: 99%

MEPE evolution in mammals reveals regions and residues of prime functional importance

Bardet¹,

Delgado²,

Sire

2009

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

In mammals, the matrix extracellular phosphoglycoprotein (MEPE) is known to activate osteogenesis and mineralization via a particular region called dentonin, and to inhibit mineralization via its ASARM (acidic serine-aspartate rich MEPE-associated motif) peptide that also plays a role in phosphatemia regulation. In order to understand MEPE evolution in mammals, and particularly that of its functional regions, we conducted an evolutionary analysis based on the study of selective pressures. Using 37 mammalian sequences we: (1) confirmed the presence of an additional coding exon in most placentals; (2) highlighted several conserved residues and regions that could have important functions; (3) found that dentonin function was recruited in a placental ancestor; and (4) revealed that ASARM function was present earlier, pushing the recruitment of MEPE deep into amniote origins. Our data indicate that MEPE was involved in various functions (bone and eggshell mineralization) prior to acquiring those currently known in placental mammals.

show abstract

“…A ação da Dentonina sobre as células-tronco da polpa foi avaliada 13 . Observou-se um aumento na taxa de proliferação dessas células, sendo possível o uso deste peptídeo na regeneração da polpa em resposta a injúrias como traumas e cáries.…”

Section: Aplicações Em Odontologiaunclassified

Células-tronco em odontologia

Soares¹,

Knop²,

Jesus

et al. 2007

Rev. Dent. Press Ortodon. Ortop. Facial

View full text Add to dashboard Cite

Introdução: existe um grande interesse no desenvolvimento de técnicas para a manipulação de células-tronco, no intuito de instituirem-se tratamentos restauradores de tecidos e órgãos. Para que a bioengenharia seja eficaz, faz-se necessária a presença de três fatores: as próprias células-tronco, uma matriz extracelular e fatores de crescimento. Existem inúmeros fatores de crescimento envolvidos no desenvolvimento do órgão dentário. Por isso pesquisadores ainda não foram capazes de formar um órgão completo, embora existam diversos estudos evidenciando a formação de esmalte e dentina a partir de células-tronco isoladas da polpa dentária. Recentemente, também foram isoladas células-tronco da polpa dos dentes decíduos. Sabe-se que estas células são altamente proliferativas, sendo de grande importância para o cirurgião-dentista o conhecimento do seu comportamento biológico e técnicas de obtenção. Objetivo: este estudo teve como objetivo realizar uma revisão de literatura acerca das atuais tendências das pesquisas com células-tronco na Odontologia, além de discorrer sobre os fatores implicados para o sucesso na utilização prática dessas células. ResumoPalavras-chave: Células-tronco. Bioengenharia. Pesquisa em Odontologia. A R T I G O I N É D I T O* Acadêmicas do Curso de Graduação em Odontologia -UFBA. ** Especialista em Prótese Dental (ABO/Ba). Mestre em Odontologia (FOUFBA). Doutorando em Biotecnologia UEFS/FIOCRUZ. *** Doutora e Mestre em Ortodontia -UFRJ. Professora Titular de Ortodontia UFBA. Diplomada pelo Board Brasileiro de Ortodontia e Ortopedia Facial. INTRODUÇÃOA perda dentária e dos tecidos periodontais pode resultar em movimento dos dentes remanescentes, dificuldade na mastigação, fonação, desequilíbrio na musculatura e comprometimento da estética dentária e do sorriso, comprometendo a auto-estima. Atualmente existem diversas terapias para substituição dos órgãos dentários, todas elas baseadas em técnicas não-biológicas e sujeitas a falhas 26 . Apesar desta condição ser uma anormalidade comum e não ameaçar a vida do paciente, esforços têm sido dirigidos para o desenvolvimento de mecanismos para a utilização de células-tronco na reposição de tecidos bucais 12 . Para a bioengenharia é essencial uma tríade composta por células-tronco ou progenitoras, uma matriz que funcione como arcabouço e proteínas sinalizadoras, denominadas fatores de crescimento, como estímulo para diferenciação celular (Fig. 1).O objetivo desta revisão de literatura foi discorrer acerca das técnicas da bioengenharia e relatar os resultados obtidos nos experimentos com células-tronco, bem como suas reais tendências na aplicação em Odontologia.

show abstract

Dentonin, a Fragment of MEPE, Enhanced Dental Pulp Stem Cell Proliferation

Cited by 66 publications

References 23 publications

Molecular Regulation of Matrix Extracellular Phosphoglycoprotein Expression by Bone Morphogenetic Protein-2

Molecular Regulation of Matrix Extracellular Phosphoglycoprotein Expression by Bone Morphogenetic Protein-2

MEPE evolution in mammals reveals regions and residues of prime functional importance

Células-tronco em odontologia

Contact Info

Product

Resources

About