Regenetiss Inc.

Tokyo, Japan

Regenetiss Inc.

Tokyo, Japan
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Harada K.,Hiroshima University | Shiba T.,Regenetiss Inc. | Shiba T.,Kitasato University | Doi K.,Hiroshima University | And 5 more authors.
PLoS ONE | Year: 2013

In response to infection, macrophages produce a series of inflammatory mediators, including nitric oxide (NO), to eliminate pathogens. The production of these molecules is tightly regulated via various mechanisms, as excessive responses are often detrimental to host tissues. Here, we report that inorganic polyphosphate [poly(P)], a linear polymer of orthophosphate ubiquitously found in mammalian cells, suppresses inducible nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, in mouse peritoneal macrophages. Poly(P) with longer chains is more potent than those with shorter chains in suppressing LPS-induced iNOS expression. In addition, poly(P) decreased LPS-induced NO release. Moreover, poly(P) suppressed iNOS mRNA expression induced by LPS stimulation, thereby indicating that poly(P) reduces LPS-induced iNOS expression by down-regulation at the mRNA level. In contrast, poly(P) did not affect the LPS-induced release of TNF, another inflammatory mediator. Poly(P) may serve as a regulatory factor of innate immunity by modulating iNOS expression in macrophages. © 2013 Harada et al.


Harada K.,Hiroshima University | Itoh H.,Regenetiss Inc. | Kawazoe Y.,Regenetiss Inc. | Miyazaki S.,YAMASA Corporation | And 5 more authors.
PLoS ONE | Year: 2013

Inorganic polyphosphate (poly(P)) has recently been found to play an important role in bone formation. In this study, we found that tartrate-resistant acid phosphatase (TRAP), which is abundantly expressed in osteoclasts, has polyphosphatase activity that degrades poly(P) and yields Pi as well as shorter poly(P) chains. Since the TRAP protein that coprecipitated with anti-TRAP monoclonal antibodies exhibited both polyphosphatase and the original phosphatase activity, poly(P) degradation activity is dependent on TRAP and not on other contaminating enzymes. The ferrous chelator α, α′-bipyridyl, which inhibits the TRAP-mediated production of reactive oxygen species (ROS), had no effect on such poly(P) degradation, suggesting that the degradation is not dependent on ROS. In addition, shorter chain length poly(P) molecules were better substrates than longer chains for TRAP, and poly(P) inhibited the phosphatase activity of TRAP depending on its chain length. The IC50 of poly(P) against the original phosphatase activity of TRAP was 9.8 mM with an average chain length more than 300 phosphate residues, whereas the IC50 of poly(P) with a shorter average chain length of 15 phosphate residues was 8.3 mM. Finally, the pit formation activity of cultured rat osteoclasts differentiated by RANKL and M-CSF were markedly inhibited by poly(P), while no obvious decrease in cell number or differentiation efficiency was observed for poly(P). In particular, the inhibition of pit formation by long chain poly(P) with 300 phosphate residues was stronger than that of shorter chain poly(P). Thus, poly(P) may play an important regulatory role in osteoclastic bone resorption by inhibiting TRAP activity, which is dependent on its chain length. © 2013 Harada et al.


Morimoto D.,Osaka University | Tomita T.,Osaka University | Kuroda S.,Osaka University | Higuchi C.,Osaka University | And 5 more authors.
Journal of Bone and Mineral Metabolism | Year: 2010

The existence of inorganic polyphosphates [poly(P)] in human cells has been demonstrated. In osteoblasts, it is suggested that the concentration of cellular poly(P) is relatively high. In this study, we examined whether poly(P) accelerates the differentiation of human mesenchymal stem cells (hMSCs) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) into osteoblastic cells. Alkaline phosphatase (ALP) activity was induced by poly(P) in hMSCs from both OA and RA. In Alizarin Red S and osteocalcin EIA, there was a significant difference between the control and poly(P) group. In real-time PCR, there was a significant difference in ALP, collagen type 1A, osteocalcin, and bone sialoprotein between the control and poly(P) group. Our findings suggest that poly(P) have the potent role of differentiating hMSCs into osteoblastic cells at the early and later stages of osteoblastic differentiation. © The Japanese Society for Bone and Mineral Research and Springer 2010.


Tsutsumi K.,Hokkaido University | Saito N.,Hokkaido University | Kawazoe Y.,Regenetiss Inc. | Ooi H.-K.,Azabu University | And 2 more authors.
PLoS ONE | Year: 2014

Since inorganic polyphosphates [poly(P)] have an activity to induce bone differenciation in vitro and in vivo, we examined an effect of poly(P) on organelle by light microscopy and electron microscopy in Murine MC3T3-E1 osteoblastic cells. The MC3T3-E1 cells were ultrastructurally observed to possess morphological characteristics of osteoblasts. Cells cultured with poly(P) were strongly stained with an anti-collagen type I antibody but not in those cultured without poly(P). Ultrastructural analysis of cells cultured with poly(P) revealed a well-developed Golgi apparatus, swollen and elongated rough endoplasmic reticulum, large mitochondria and many coated pits. Since MC3T3-E1 cells can be transformed from a resting phase to an active blastic cell phase after supplementation with poly(P), it implies that poly(P) can be an effective material for bone regeneration. © 2014 Tsutsumi et al.


Patent
Regenetiss Inc. | Date: 2014-08-10

The object of the present invention is to provide an oral composition, which can remove tooth stain effectively. The object of the present invention is also to provide an oral composition, which scarcely damages teeth and gums and can be easily applied. An oral composition for removing tooth stain, which comprises 3.5 to 30% by weight of peroxide and 5 to 20% by weight of phosphate polymer (in particular, ultraphosphate having an average chain length of phosphoric acid polymerization of 10 to 30).


Patent
Regenetiss Inc. | Date: 2011-09-22

[Problem] The object of the present invention is to provide an oral composition, which can remove tooth stain effectively. The object of the present invention is also to provide an oral composition, which scarcely damages teeth and gums and can be easily applied. [Method of solution] An oral composition for removing tooth stain, which comprises 3.5 to 30% by weight of peroxide and 5 to 20% by weight of phosphate polymer (in particular, ultraphosphate having an average chain length of phosphoric acid polymerization of 10 to 30).


Patent
RegeneTiss Inc., Mmt Co. and Ochi | Date: 2010-05-05

Disclosed are: a peptide capable of binding to an immunoglobulin; a fusion protein of the peptide; nucleic acids encoding the peptide and the fusion protein, respectively; production methods for the peptide and the fusion protein, respectively; a composition and a means for binding an immunoglobulin; a pharmaceutical composition for the treatment or prevention of a disease induced by the binding between C1q and an immunoglobulin, which comprises a peptide capable of binding to the immunoglobulin or a fusion protein of the peptide; and others.


Patent
Regenetiss Inc. | Date: 2012-09-26

A tooth whitening composition with a high level of whitening effectiveness over the entire tooth whitening composition application includes colloidal platinum as a platinum catalyst in a peroxide-containing oral composition. Whitening effectiveness can be enhanced by application of a tooth whitening composition containing colloidal platinum to the teeth surface followed by photo-irradiation of the application site.


PubMed | Regenetiss Inc., Kitasato University, Azabu University and Hokkaido University
Type: Journal Article | Journal: PloS one | Year: 2014

Since inorganic polyphosphates [poly(P)] have an activity to induce bone differenciation in vitro and in vivo, we examined an effect of poly(P) on organelle by light microscopy and electron microscopy in Murine MC3T3-E1 osteoblastic cells. The MC3T3-E1 cells were ultrastructurally observed to possess morphological characteristics of osteoblasts. Cells cultured with poly(P) were strongly stained with an anti-collagen type I antibody but not in those cultured without poly(P). Ultrastructural analysis of cells cultured with poly(P) revealed a well-developed Golgi apparatus, swollen and elongated rough endoplasmic reticulum, large mitochondria and many coated pits. Since MC3T3-E1 cells can be transformed from a resting phase to an active blastic cell phase after supplementation with poly(P), it implies that poly(P) can be an effective material for bone regeneration.


PubMed | Regenetiss Inc., University of Toronto and Mt Sinai Hospital
Type: | Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society | Year: 2016

Disc degeneration is associated with low back pain for which currently there is no optimal therapy so there is a great need to identify new treatment approaches. Inorganic polyphosphates (polyP) are linear polymers of orthophosphate units varying in chain length and present in many cell types. As polyP has anabolic effects on chondrocytes, we hypothesized that polyP treatment would enhance matrix accumulation by nucleus pulposus (NP) cells. NP cells isolated from bovine caudal discs were grown in 3D culture under normoxic or in select experiments under hypoxic conditions, in the presence or absence of various concentrations and sizes of polyP. Gene expression was determined using RT-PCR. Matrix accumulation was quantified by measuring proteoglycan and collagen contents. DAPI fluorescence shift was used to stain for polyP in tissue. DAPI staining showed polyP present predominantly in the pericellular region of in vitro formed tissue. PolyP treatment enhanced matrix accumulation in a concentration and chain length dependant manner. NP cells exposed to polyP-22 (22 phosphate units length) showed an increase in gene expression of aggrecan, Collagen II, Sox 9 and MMP-13 which was maintained for the 14 days of culture This suggests that polyP may enhance NP tissue formation in vitro by upregulating the expression of matrix genes. As polyP enhances proteoglycan accumulation even under hypoxic conditions, this raises the possibility that polyP may be a novel treatment to induce NP regeneration. This article is protected by copyright. All rights reserved.

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