scholarly journals Critical Regulation of Bone Morphogenetic Protein-induced Osteoblastic Differentiation by Delta1/Jagged1-activated Notch1 Signaling

2005 ◽  
Vol 280 (16) ◽  
pp. 15842-15848 ◽  
Author(s):  
Masuhiro Nobta ◽  
Tomoo Tsukazaki ◽  
Yasuaki Shibata ◽  
Chang Xin ◽  
Takeshi Moriishi ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Notch Signaling ◽  
Bone Morphogenetic Protein ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Notch Pathway ◽  
Osteoblastic Differentiation ◽  
Differentiation Markers ◽  
Induced Differentiation ◽  
Morphogenetic Protein

Functional involvement of the Notch pathway in osteoblastic differentiation has been previously investigated using the truncated intracellular domain, which mimics Notch signaling by interacting with the DNA-binding protein CBF-1. However, it is unclear whether Notch ligands Delta1 and Jagged1 also induce an identical cellular response in osteoblastic differentiation. We have shown that both Delta1 and Jagged1 were expressed concomitantly with Notch1 in maturating osteoblastic cells during bone regeneration and that overexpressed and immobilized recombinant Delta1 and Jagged1 alone did not alter the differentiated state of MC3T3-E1 and C2C12 cells. However, they augmented bone morphogenetic protein-2 (BMP2)-induced alkaline phosphatase activity and the expression of several differentiation markers, except for osteocalcin, and ultimately enhanced calcified nodule andin vivoectopic bone formation of MC3T3-E1. In addition, both ligands transmitted signal through the CBF-1-dependent pathway and stimulated the expression of HES-1, a direct target of Notch pathway. To test the necessity of Notch signaling in BMP2-induced differentiation, Notch signaling was inhibited by the dominant negative extracellular domain of Notch1, specific inhibitor, or small interference RNA. These treatments decreased alkaline phosphatase activity as well as the expression of other differentiation markers and inhibited the promoter activity of Id-1, a target gene of the BMP pathway. These results indicate the functional redundancy between Delta1 and Jagged1 in osteoblastic differentiation whereby Delta1/Jagged1-activated Notch1 enhances BMP2-induced differentiation through the identical signaling pathway. Furthermore, our data also suggest that functional Notch signaling is essential not only for BMP2-induced osteoblast differentiation but also for BMP signaling itself.

scholarly journals Roles of Bone Morphogenetic Protein Type I Receptors and Smad Proteins in Osteoblast and Chondroblast Differentiation

1999 ◽  
Vol 10 (11) ◽  
pp. 3801-3813 ◽  
Author(s):  
Makiko Fujii ◽  
Kohsuke Takeda ◽  
Takeshi Imamura ◽  
Hiromasa Aoki ◽  
T. Kuber Sampath ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Morphogenetic Protein ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Chondrogenic Differentiation ◽  
C2c12 Cells ◽  
Vector System ◽  
Type I ◽  
Morphogenetic Protein ◽  
Smad Proteins

The biological effects of type I serine/threonine kinase receptors and Smad proteins were examined using an adenovirus-based vector system. Constitutively active forms of bone morphogenetic protein (BMP) type I receptors (BMPR-IA and BMPR-IB; BMPR-I group) and those of activin receptor–like kinase (ALK)-1 and ALK-2 (ALK-1 group) induced alkaline phosphatase activity in C2C12 cells. Receptor-regulated Smads (R-Smads) that act in the BMP pathways, such as Smad1 and Smad5, also induced the alkaline phosphatase activity in C2C12 cells. BMP-6 dramatically enhanced alkaline phosphatase activity induced by Smad1 or Smad5, probably because of the nuclear translocation of R-Smads triggered by the ligand. Inhibitory Smads, i.e., Smad6 and Smad7, repressed the alkaline phosphatase activity induced by BMP-6 or the type I receptors. Chondrogenic differentiation of ATDC5 cells was induced by the receptors of the BMPR-I group but not by those of the ALK-1 group. However, kinase-inactive forms of the receptors of the ALK-1 and BMPR-I groups blocked chondrogenic differentiation. Although R-Smads failed to induce cartilage nodule formation, inhibitory Smads blocked it. Osteoblast differentiation induced by BMPs is thus mediated mainly via the Smad-signaling pathway, whereas chondrogenic differentiation may be transmitted by Smad-dependent and independent pathways.

IL-6 Induces Osteoblastic Differentiation of Periodontal Ligament Cells

2008 ◽  
Vol 87 (10) ◽  
pp. 937-942 ◽  
Author(s):  
K. Iwasaki ◽  
M. Komaki ◽  
K. Mimori ◽  
E. Leon ◽  
Y. Izumi ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Ascorbic Acid ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Periodontal Ligament ◽  
Kinase Inhibitors ◽  
Osteoblastic Differentiation ◽  
Mitogen Activated Protein Kinase ◽  
Periodontal Ligament Cells ◽  
Igf I

Interleukin (IL)-6 has been considered as an osteolytic factor involved in periodontal disease. However, the function of IL-6 in osteoblastic differentiation of periodontal ligament cells is not clear. We examined the effects of IL-6 and its soluble receptor (sIL-6R) on osteoblastic differentiation of periodontal ligament cells. Osteoblastic differentiation was induced by ascorbic acid. Osteoblast markers, including alkaline phosphatase activity and Runx2 gene expression, were examined. The mechanism of action of IL-6 on osteoblastic differentiation was evaluated by insulin-like growth factor (IGF)-I production and specific inhibitors for the IL-6-signaling molecule. IL-6/sIL-6R enhanced alkaline phosphatase activity and Runx2. Alkaline phosphatase activity was reduced by anti-IGF-I antibody. Mitogen-activated protein kinase and Janus protein tyrosine kinase inhibitors diminished alkaline phosphatase induced by IL-6/sIL-6R. We conclude that IL-6/sIL-6R increases ascorbic-acid-induced alkaline phosphatase activity through IGF-I production, implying that IL-6 acts not only as an osteolytic factor, but also as a mediator of osteoblastic differentiation in periodontal ligament cells.

Inorganic Polyphosphate: a Possible Stimulant of Bone Formation

2007 ◽  
Vol 86 (9) ◽  
pp. 893-897 ◽  
Author(s):  
Y. Hacchou ◽  
T. Uematsu ◽  
O. Ueda ◽  
Y. Usui ◽  
S. Uematsu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Alveolar Bone ◽  
Bone Mineralization ◽  
Osteoblastic Differentiation ◽  
Inorganic Polyphosphate ◽  
Pit Formation

Inorganic polyphosphates [Poly(P)] are often distributed in osteoblasts. We undertook the present study to verify the hypothesis that Poly(P) stimulates osteoblasts and facilitates bone formation. The osteoblast-like cell line MC 3T3-E1 was cultured with Poly(P), and gene expression and potential mineralization were evaluated by reverse-transcription polymerase chain-reaction. Alkaline phosphatase activity, von Kossa staining, and resorption pit formation analyses were also determined. The potential role of Poly(P) in bone formation was assessed in a rat alveolar bone regeneration model. Poly(P) induced osteopontin, osteocalcin, collagen 1α, and osteoprotegerin expression and increased alkaline phosphatase activity in MC 3T3-E1 cells. Dentin slice pit formation decreased with mouse osteoblast and bone marrow macrophage co-cultivation in the presence of Poly(P). Promotion of alveolar bone regeneration was observed locally in Poly(P)-treated rats. These findings suggest that Poly(P) plays a role in osteoblastic differentiation, activation, and bone mineralization. Thus, local poly(P) delivery may have a therapeutic benefit in periodontal disease.

scholarly journals Modulation of connexin43 alters expression of osteoblastic differentiation markers

2006 ◽  
Vol 290 (4) ◽  
pp. C1248-C1255 ◽  
Author(s):  
Zhongyong Li ◽  
Zhiyi Zhou ◽  
Marnie M. Saunders ◽  
Henry J. Donahue
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Intercellular Communication ◽  
Cell Communication ◽  
Osteoblastic Differentiation ◽  
Type I ◽  
Mrna Levels ◽  
Gap Junctional Intercellular Communication ◽  
Gap Junctional

Gap junctional channels between cells provide a pathway for exchange of regulatory ions and small molecules. We previously demonstrated that expression of connexins and cell-to-cell communication parallel osteoblastic differentiation and that nonspecific pharmacological inhibitors of gap junctional communication inhibit alkaline phosphatase activity. In this study, we stably transfected connexin (Cx)43 antisense cDNA into the immortalized human fetal osteoblastic cell line hFOB 1.19 (hFOB/Cx43−). hFOB/Cx43− cells express lower levels of Cx43 protein and mRNA and display a 50% decrease in gap junctional intercellular communication relative to control [hFOB/plasmid vector control (pvc)]. This suggests that other connexins, such as Cx45, which is expressed to a similar degree in hFOB/Cx43− cells and hFOB/pvc cells, contribute to cell-to-cell communication in hFOB 1.19 cells. We observed almost total inhibition of alkaline phosphatase activity in hFOB/Cx43− cells despite only a 50% decrease in cell-to-cell communication. This suggests the intriguing possibility that Cx43 expression per se, independent of cell-to-cell communication, influences alkaline phosphatase activity and perhaps bone cell differentiation. Quantitative real-time RT-PCR revealed that mRNA levels for osteocalcin and core binding factor α1 (Cbfa1) increased as a function of time in hFOB/pvc but were inhibited in hFOB/Cx43−. Osteopontin mRNA levels were increased in hFOB/Cx43− relative to hFOB/pvc and decreased as a function of time in both hFOB/Cx43− and hFOB/pvc. Transfection with Cx43 antisense did not affect expression of type I collagen in hFOB 1.19 cells. These results suggest that gap junctional intercellular communication and expression of Cx43 contribute to alkaline phosphatase activity, as well as osteocalcin, osteopontin, and Cbfa1 expression in osteoblastic cells.

Penicillic Acid Congener, a New Inhibitor of BMP-Induced Alkaline Phosphatase Activity in Myoblasts, Produced by the Fungus Penicillium sp. BF-0343

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2094265
Author(s):  
Nobuhiro Koyama ◽  
Yasuhiro Otoguro ◽  
Satoshi Ohte ◽  
Takenobu Katagiri ◽  
Hiroshi Tomoda
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Spectroscopic Data ◽  
Inhibitory Concentration ◽  
Culture Broth ◽  
Penicillic Acid ◽  
Penicillium Sp ◽  
Morphogenetic Protein

During our screening for microbial regulators of bone metabolism, a new compound, 6-ethoxy-5,6-dihydropenillic acid (1), was isolated together with a known and structurally related penicillic acid (2) from the culture broth of the soil-derived fungus Penicillium sp. BF-0343. The structure of 1 was elucidated by various spectroscopic data including nuclear magnetic resonance experiments. Compounds 1 and 2 dose-dependently inhibited bone morphogenetic protein–induced alkaline phosphatase activity in myoblasts with half-maximal inhibitory concentration values of 19.8 and 2.1 μM, respectively.

17β-Oestradiol enhances the stimulatory effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity in human osteosarcoma SaOS-2 cells in a differentiation-dependent manner

1996 ◽  
Vol 148 (1) ◽  
pp. 181-187 ◽  
Author(s):  
L G Rao ◽  
J N Wylie ◽  
M S Kung Sutherland ◽  
T M Murray
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Osteoblastic Differentiation ◽  
Interactive Effects ◽  
Maximal Response ◽  
Dependent Manner ◽  
Human Osteosarcoma ◽  
Differentiated Cells ◽  
Dose Dependent

Abstract We tested the effect of osteoblastic differentiation on the interactive effects of 17β-oestradiol (E2) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on alkaline phosphatase activity. As cell models we utilized the more differentiated human osteosarcoma (SaOS) cells that had been cultured for 6 days in medium containing 10 nm dexamethasone (Dex) (SaOS+Dex cells) and the less differentiated cells cultured in the absence of Dex (SaOS−Dex cells). The cells were challenged with 1,25(OH)2D3 in the presence or absence of Dex for 24 h and then with E2 for an additional 24 h. In SaOS−Dex cells, alkaline phosphatase activity remained constant over the 48-h period and was not significantly affected by E2, 1,25(OH)2D3 or 1,25(OH)2D3+E2 treatment. On the other hand, in SaOS+Dex cells, 1,25(OH)2D3 and E2+1,25(OH)2D3 stimulated alkaline phosphatase activity (ANOVA, F= 154·2, P<0·0001) with the maximal response at 48 h (P<0·01). In SaOS+Dex cells, 1,25(OH)2D3 had dose-dependent stimulatory effects which were strongly enhanced by 10 nm E2 (ANOVA, F=46·0, P<0·001). Studies on dose-dependent effects of E2, in the presence or absence of 100 nm 1,25(OH)2D3, revealed that in the presence of 1,25(OH)2D3, the E2 dose-response curve was biphasic in SaOS+Dex cells (ANOVA, F=3·40, P<0·005), with maximum stimulation at 10 nm E2 (P<0·01). The specificity of E2 was verified using the inactive 17α-oestradiol and the oestrogen antagonist, tamoxifen. These data indicate that E2 and 1,25(OH)2D3 have positive interactive effects on alkaline phosphatase activity in human osteoblasts, and suggest that the expression of this interaction is dependent on the stage of differentiation of the cells. Journal of Endocrinology (1996) 148, 181–187

LEUCOCYTE METABOLISM IN PREGNANCY

1960 ◽  
Vol XXXV (IV) ◽  
pp. 575-584 ◽  
Author(s):  
C. Borel ◽  
J. Frei ◽  
A. Vannotti
Keyword(s):  
Alkaline Phosphatase ◽  
Oxygen Consumption ◽  
Pregnant Women ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Lactate Production ◽  
Glucose Consumption ◽  
In Pregnancy

ABSTRACT Enzymatic studies, on leucocytes of pregnant women, show an increase of the alkaline phosphatase activity and a decrease of the glucose consumption and lactate production, as well as of proteolysis. The oxygen consumption, with succinate as substrate, does not vary.

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