Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Research Abstract Details 

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Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Abstract Text:

M Sugiyama,T Kodama,K Konishi,K Abe,S Asami,S Oikawa,

Bone morphogenetic protein (BMP)-2, a member of the BMP family, plays an important role in osteoblast differentiation and bone formation. To discover small molecules that induce BMP-2, a luciferase reporter vector containing the 5'-flanking promoter region of the human BMP-2 gene was constructed and transfected into human osteosarcoma (HOS) cells. By the screening of an in-house natural product library with stably transfected HOS cells, a fungal metabolite, compactin, known as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was isolated. The stimulation of the promoter activity by compactin seemed to be specific for BMP-2 gene in HOS cells, since it had little effect on BMP-4 or SV40 promoter activity and the stimulation was not observed in Chinese hamster ovary (CHO) cells. RT-PCR analysis and alkaline phosphatase assay revealed that compactin induced an increase in the expression of BMP-2 mRNA and protein. Like compactin, simvastatin also activated the BMP-2 promoter, whereas pravastatin did not. The statin-mediated activation of BMP-2 promoter was completely inhibited by the downstream metabolite of HMG-CoA reductase, mevalonate, indicating that the activation was a result of the inhibition of the enzyme. These results suggest that statins, if they are selectively targeted to bone, have beneficial effects in the treatment of osteoporosis or bone fracture.

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Publishing Authors By Initials

M Sugiyama,T Kodama,K Konishi,K Abe,S Asami,S Oikawa,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemical and biophysical research communication

VOLUME: 271

Page Numbers: 688-92

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 0006-291X

DAY: 19

MONTH: May

YEAR: 2000

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372516

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Information

Substance Name: Pravastatin

Registry Number: 81093-37-0

Grant and Affiliation Information for Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.

AFFILIATION: Suntory Biomedical Research Limited, Suntory Institute for Fundamental Research, 1-1-1 Wakayamadai, Osaka, Shimamoto-cho, Mishima-gun, 618-8503, Japan.

Country: UNITED STATES

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MEDLINETA: Biochem Biophys Res Commun

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