scholarly journals Trichocyalides A and B, new inhibitors of alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblasts, produced by Trichoderma sp. FKI-5513

2012 ◽  
Vol 65 (11) ◽  
pp. 565-569 ◽  
Author(s):  
Takashi Fukuda ◽  
Ryuji Uchida ◽  
Satoshi Ohte ◽  
Hiroyo Inoue ◽  
Hiroyuki Yamazaki ◽  
...  
2005 ◽  
Vol 280 (16) ◽  
pp. 15842-15848 ◽  
Author(s):  
Masuhiro Nobta ◽  
Tomoo Tsukazaki ◽  
Yasuaki Shibata ◽  
Chang Xin ◽  
Takeshi Moriishi ◽  
...  

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.


1999 ◽  
Vol 10 (11) ◽  
pp. 3801-3813 ◽  
Author(s):  
Makiko Fujii ◽  
Kohsuke Takeda ◽  
Takeshi Imamura ◽  
Hiromasa Aoki ◽  
T. Kuber Sampath ◽  
...  

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.


2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2094265
Author(s):  
Nobuhiro Koyama ◽  
Yasuhiro Otoguro ◽  
Satoshi Ohte ◽  
Takenobu Katagiri ◽  
Hiroshi Tomoda

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.


1960 ◽  
Vol XXXV (IV) ◽  
pp. 575-584 ◽  
Author(s):  
C. Borel ◽  
J. Frei ◽  
A. Vannotti

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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