2002 Fiscal Year Final Research Report Summary
Study on the effects of statin on growth and differentiation of cartilage
| Project/Area Number |
13671938
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
NOSHIRO Mitsuhide Hiroshima Univ. Grad. Sch. Biomed. Sci., Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (00144858)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Cholesterol / statin / chondrocyte / stem cell / BMP / circadian rhythm / DEC1 / DEC2 |
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| Research Abstract |
Statin compounds are reported to activate BMP-2 gene expression and to generate the bone formation as a result. Statins are originally known to be inhibitors for HMG CoA reductase that strongly lower plasma cholesterol and triglycerides levels in human and animals and are used for the therapy of hypercholesterolemia. In this study, stains, serivastatin and pravastatin are examined for their action on growth and differentiation of cartilage.
Several cDNA probes are generated from human and rabbit to examine the differentiation markers. Using these porbes, the effects of statins on primary cultures of chondrocytes and stem cells from rabbits were determined and following results were obtained.
Pravastatin increased the Jevel of BMP-2 mRNA in rabbit chondrocytes for 24 h at 10^<-5> M.
Serivastatin did not affect the level of BMP-2 mRNA in rabbit stem cells at 10^<-6> M, whereas it markedly increased the level of Indian hedgehog mRNA concomitantly increment of levels of PTHrP and alkaline phosphatase mRNA was observed. Calcification was observed at 5x10^<-5> M.
In the course of this study, novel basic helix-loop-helix transcription factors, DEC1 and DEC2, were isolated and proved to be involved in the regulation of chondrocyte differentiation. DEC1 and DEC2 were ubiquitously expressed in various organs and exhibit multiple functions including new members of molecular clock regulation circadian rhythm of animals. The rhythmic expression of DEC1 and DEC2 were also observed in cartilage indicating the importance of rhythmic regulation of chondrocyte growth and differentiation.
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[Publications] Katsumi Fujimoto, Ming Shen, Mitsuhide Noshiro^*, Kazumi Matsubara, Sohei Shingu, Kiyomasa Honda, Eri Yoshida, Ketut Suardita, Yoichi Matsuda, and Yukio Kato: "Molecular Cloning and Characterization of DEC2, a New Member of Basic Helix-Loop-Helix Proteins"Biochem.Biophys.Res.Commun.. 260. 164-171 (2001)
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[Publications] Nakamasu, K., Kawamoto, T., Yoshida, E., Noshiro, M., Matsuda, Y. and Kato, Y.: "Structure and Promoter Analysis of the Mouse Membrane-bound Transferrin-like Protein (MTf) Gene"Eur.J.Biochem.. 268. 1468-1476 (2001)
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[Publications] Yoshida, E. Noshiro, M., Kawamoto, T., Tsutumi, S., Kurata, Y., and Kato, Y.: "Direct Inhibition of Indian Hedgehog Expression by Parathyroid Hormone (PTH)/PTH-Related Peptide and Up-Regulation by Retinoic Acid in Growth Plate Chondrocyte Cultures"Exp.Cell Res.. Vol.265, No.1, Apr. 64-72 (2001)
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