MEPE is downregulated as dental pulp stem cells differentiate

Li, He; Wu, Li; Shi, Songtao; Habelitz, Stefan; Gao, Canzhu; DenBesten, Pamela

doi:10.1016/j.archoralbio.2005.03.003

Cited by 67 publications

(68 citation statements)

References 36 publications

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“…Cells were then either stained with Alizarin red-S or used for RNA extraction. Alizarin red-S stain was extracted with 10% cetylpyridinium chloride and quantified by absorbance measurement at 562 nm as previously described (Liu et al 2005a).…”

Section: Bone Marrow Stromal Cell (Bmsc) Culturementioning

confidence: 99%

Phosphorylated acidic serine–aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity

Liu

Rowe

Vierthaler

et al. 2007

Journal of Endocrinology

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Inactivating PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome) mutations cause X-linked hypophosphatemia in humans and mice (Hyp) through overproduction of fibroblast growth factor 23 (FGF23) a phosphaturic factor, by osteocytes. Matrix extracellular phosphoglycoprotein (MEPE) is also elevated in Hyp and other hypophosphatemic disorders. In addition, the administration of an ASARM (acidic serineaspartate rich MEPE-associated motif) peptide derived from MEPE causes phosphaturia and inhibits bone mineralization in mice, suggesting that MEPE also plays a role in phosphate homeostasis. Since recent studies found that MEPE binds specifically to PHEX in vitro, we tested the effect of recombinant-MEPE and its ASARM peptide on PHEX enzyme activity in vitro and FGF23 expression in bone marrow stromal cell cultures ex vivo. We found that both recombinant MEPE and synthetic phosphorylated ASARM peptide (ASARM-PO 4 ) inhibit PHEX enzyme activities in an in vitro fluorescent-quenched PHEX enzyme activity assay. The ASARM-PO 4 peptide inhibits PHEX enzyme activity in a dose-dependent manner with a K i of 128 nM and V maxKi of 100%. Recombinant MEPE also inhibits PHEX activity (K i Z2 nM and V maxKi Z26%). Long-term bone marrow stromal cell cultures supplemented with 10 mM ASARM-PO 4 peptide resulted in significant elevation of FGF23 transcripts and inhibition of mineralization. These findings suggest that MEPE inhibits mineralization and PHEX activity and leads to increased FGF23 production. The resulting coordination of mineralization and release of a phosphaturic factor by MEPE may serve a physiological role in regulating systemic phosphate homeostasis to meet the needs for bone mineralization.

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Section: Bone Marrow Stromal Cell (Bmsc) Culturementioning

confidence: 99%

Phosphorylated acidic serine–aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity

Liu

Rowe

Vierthaler

et al. 2007

Journal of Endocrinology

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“…Primers for collagen type-3, FABP 4 , and cartilage-specific proteoglycan core protein (aggrecan) genes were designed by using Primer-BLAST online software from the National Center for Biotechnology (Bethesda, MD) and synthesized by Invitrogen. Other primer sequences were used as described elsewhere, 23,24 and Table 1 delineates primers that were used in this study.…”

Section: Real-time (Rt) Polymerase Chain-reaction (Pcr) Analysismentioning

confidence: 99%

“…The tooth germ (or tooth bud) is an aggregation of progenitor cells that forms a tooth, consisting of the dental papilla, the dental follicle, and the enamel organ. 4 Tooth germs of third molars were reported to develop after the age of 6 years, but remain undifferentiated before this time. This may explain why MSCs derived from third molars are highly proliferative and multipotent.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers

Doğan¹,

Yalvaç²,

Şahın³

et al. 2012

IJN

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Stem cell usage provides novel avenues of tissue regeneration and therapeutics across disciplines. Apart from ethical considerations, the selection and amplification of donor stem cells remain a challenge. Various biopolymers with a wide range of properties have been used extensively to deliver biomolecules such as drugs, growth factors and nucleic acids, as well as to provide biomimetic surface for cellular adhesion. Using human tooth germ stem cells with high proliferation and transformation capacity, we have investigated a range of biopolymers to assess their potential for tissue engineering. Tolerability, toxicity, and their ability to direct differentiation were evaluated. The majority of pluronics, consisting of both hydrophilic and hydrophobic poly(ethylene oxide) chains, either exerted cytotoxicity or had no significant effect on human tooth germ stem cells; whereas F68 increased the multi-potency of stem cells, and efficiently transformed them into osteogenic, chondrogenic, and adipogenic tissues. The data suggest that differentiation and maturation of stem cells can be promoted by selecting the appropriate mechanical and chemical properties of polymers. It has been shown for the first time that F68, with its unique molecular characteristics, has a great potential to increase the differentiation of cells, which may lead to the development of new tissue engineering strategies in regenerative medicine.

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“…The asymmetric division of SC produces a SC daughter to maintain the stem cell pool and a transient amplifying (TA) daughter that differentiates after a limited number of divisions. Odontoblasts committed to differentiation express an Msx1 homeobox protein [20] that is downregulated as cells enter the early differentiation stage, which is marked by the appearance of matrix extracellular phosphoglycoprotein (MEPE) [21,22]. MEPE must be downregulated for the late differentiation markers, including dentin sialoprotein (DSP), to be upregulated [1,[21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

Vandomme

Touil

Ostyn

et al. 2014

Stem Cells and Development

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Dental pulp stem cells (DPSCs) remain quiescent until activated in response to severe dental pulp damage. Once activated, they exit quiescence and enter regenerative odontogenesis, producing reparative dentin. The factors and signaling molecules that control the quiescence/activation and commitment to differentiation of human DPSCs are not known. In this study, we determined that the inhibition of insulin-like growth factor 1 receptor (IGF-1R) and p38 mitogen-activated protein kinase (p38 MAPK) signaling commonly activates DPSCs and promotes their exit from the G0 phase of the cell cycle as well as from the pyronin Y low stem cell compartment. The inhibition of these two pathways, however, inversely determines DPSC fate. In contrast to p38 MAPK inhibitors, IGF-1R inhibitors enhance dental pulp cell sphere-forming capacity and reduce the cells' colony-forming capacity without inducing cell death. The inverse cellular changes initiated by IGF-1R and p38 MAPK inhibitors were accompanied by inverse changes in the levels of active signal transducer and activator of transcription 3 (STAT3) factor, inactive glycogen synthase kinase 3, and matrix extracellular phosphoglycoprotein, a marker of early odontoblast differentiation. Our data suggest that there is cross talk between the IGF-1R and p38 MAPK signaling pathways in DPSCs and that the signals provided by these pathways converge at STAT3 and inversely regulate its activity to maintain quiescence or to promote self-renewal and differentiation of the cells. We propose a working model that explains the possible interactions between IGF-1R and p38 MAPK at the molecular level and describes the cellular consequences of these interactions. This model may inspire further fundamental study and stimulate research on the clinical applications of DPSC in cellular therapy and tissue regeneration.

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MEPE is downregulated as dental pulp stem cells differentiate

Cited by 67 publications

References 36 publications

Phosphorylated acidic serine–aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity

Phosphorylated acidic serine–aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity

Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

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