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Simvastatin이 UMR-106 세포의 조골세포 형성에 미치는 영향.

Effects of Simvastatin on osteogenesis of rat osteoblast-like cells, UMR-106

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Purpose : The purpose of this study is to investigate the effects of Simvastatin, which is HMG-CoA reductase inhibitor, on proliferation and differentiation of osteoblast. Materials & Methods : Twenty-four cell culture plates containing essential medium were seeded with UMR-106 cell lines, at density of 5 x 104 cells per plate. Each plates were incubated with 5% CO2 incubator at 37℃. Starting from 2 days after incubation, cell culture medias were replaced with Osteogenesis induction media every 2 days, for 12 days. In some plates, 0.01, 0.1, 1, 10, 100μM of Simvastatin were added with Osteogenesis induction media, and classified as "test group". Those not added with Simvastatin were classified as "control group". Results : 1. When Alrizarin Red staining was observed with naked eye, control group showed normal deep red color, but test group show rapid decrease of red color as Simvastatin concentration increased more than 0.1μM. 2, When observed with microscope, compared to control group, amount of osteo matrix stained with Alrizarin Red decreased rapidly in Simvastatin concentration more than 0.1μM. 3. In optical density analysis, regarding control group as a basis, mineral deposition decreased rapidly when Simvastatin concentration increased more than 0.1μM. 4. In flow cytometry analysis, survival rate of UMR-106 cell showed no changes in both control group and test group. Conclusion : From the above results, we were able to identify that Simvastatin inhibited osteogenesis without effecting survival or cell number of osteoblasts.

Abstract

Purpose : The purpose of this study is to investigate the effects of Simvastatin, which is HMG-CoA reductase inhibitor, on proliferation and differentiation of osteoblast. Materials & Methods : Twenty-four cell culture plates containing essential medium were seeded with UMR-106 cell lines, at density of 5 x 104 cells per plate. Each plates were incubated with 5% CO2 incubator at 37℃. Starting from 2 days after incubation, cell culture medias were replaced with Osteogenesis induction media every 2 days, for 12 days. In some plates, 0.01, 0.1, 1, 10, 100μM of Simvastatin were added with Osteogenesis induction media, and classified as "test group". Those not added with Simvastatin were classified as "control group". Results : 1. When Alrizarin Red staining was observed with naked eye, control group showed normal deep red color, but test group show rapid decrease of red color as Simvastatin concentration increased more than 0.1μM. 2, When observed with microscope, compared to control group, amount of osteo matrix stained with Alrizarin Red decreased rapidly in Simvastatin concentration more than 0.1μM. 3. In optical density analysis, regarding control group as a basis, mineral deposition decreased rapidly when Simvastatin concentration increased more than 0.1μM. 4. In flow cytometry analysis, survival rate of UMR-106 cell showed no changes in both control group and test group. Conclusion : From the above results, we were able to identify that Simvastatin inhibited osteogenesis without effecting survival or cell number of osteoblasts.

참고문헌 (32)

  1. "ZORCO􄠶(SIMVASTATIN); DISCRIPTION", MERCK & CO., INC
  2. Hunninghake DB, "Therapeutic efficacy of the lipidlowering armamentarium: the clinical benefits of aggressive lipid-lowering therapy", Am J Med, 104, pp.9~13 (1998)
  3. Rogers MJ, "Statins: lower lipids and better bones?", Nature Medicine, 6, pp.21~23 (2000)
  4. Mundy G, "Stimulation of Bone Formation in Vitro and Rodents by Statins", Science, 286, pp.1946~1949 (1999)
  5. Maeda T, "Statins Augment Vascular Endothelial Growth Factor Expression in Osteoblastic Cells via Inhibition of Protein Prenylation", Endocrinology, 144, pp.681~692 (2003)
  6. Hwang RJ, "Calcyclin, a Ca2+ Ion-binding Protein, Contributes to the Anabolic Effects of Simvastatin on Bone", J Biological Chemistr, 279, pp.21239~21247 (2004)
  7. Edwards CJ, "Statin as modulators of bone formation", Arthritis Res, 1, pp.151~153 (2002)
  8. Parhami F, "Role of Cholesterol Biosynthetic Pathway in Osteoblastic Differentiation of Marrow Stromal Cells", J bone Miner Res, 17, pp.1997~2003 (2002)
  9. Nuckolls GH, "Lovastatin promotes cartilage growth but inhibits endochondral ossification of cranial base in organ culture", J Bone Miner Res, 15, pp.1~ (2000)
  10. von Stechow D, "Does simvastatin stimulate bone formation in vivo?", BMC Musculoskeletal Disorder, 4, pp.8~17 (2003)
  11. van Staa TP, "Use of Statins and Risk of Fractures", JAMA, 285, pp.1850~1855 (2001)
  12. Rejnmark L, "Effects of Simvastatin on Bone Turnover and BMD: A 1-Year Randomized Controlled Trial in Postmenopausal Osteopenic Women", J Bone Miner Res, 19, pp.737~744 (2004)
  13. Wu B, "Paradoxical Effects of Statins on Aortic Valve Myofibroblasts and Osteoblasts Implication for End-stage Vascular Heart Disease", Arterioscler Thromb Vasc Biol, 25, pp.592~597 (2005)
  14. Beak KH, "The Effect of Simvastatin on the Proliferation and Differentiation of Human Bone Marrow Stromal Cells", J Korean Med Sci, 20, pp.438~444 (2005)
  15. Maritz FJ, "Effect of statin on Bone Mineral Density and Bone Histomorphometry in Rodents", Arterioscler Thromb Vasc Biol, 21, pp.1636~1641 (2001)
  16. Garrett R, "The role of statins as potential targets for bone formation", Arthritis Res, 4, pp.237~240 (2002)
  17. Choudhury NG, "Statin-induced Ras Activation Integrates the Phosphatidylinositol 3-Kinase Signal to Akt and MAPK for Bone Morphogenetic Protein-2 Expression in Osteoblast Differentiation", The Journal of Biological Chemistry, 282, pp.4938~4993 (2007)
  18. Midy V, "Vasculotropin", vascular endothelial growth factor induces differentiation in cultured osteoblasts, 1994, pp.199, 380~386
  19. Maeda T, "Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells", Biochem Biophys Res Commun, 280, pp.874~877 (2001)
  20. Partridge NC, "Morphological and biochemical characterization of four clonal osteogenic sarcoma cell lines of rat origin", Cancer Research, 43, pp.4308~4314 (1983)
  21. Rajamannan NM, "Atorvastatin Inhibits Hypercholersterolemia- Induced Cellular Proliferation and Bone Matrix Production in the Rabbit", 2002, 105, pp.2660~2665 (2002)
  22. Novaro GM, "Effect of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors on the Progression of Calcific Aortic Stenosis", Circulation, 104, pp.2205~2209 (2001)
  23. Takemoto M, "Pleiotropic Effects of 3- Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors", Arterioscler Thromb Vasc Biol, 21, pp.1712~1719 (2001)
  24. Yao W, "Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats", J Musculoskeletal Neuronal Interact, 6(3), pp.277~283 (2006)
  25. Casey PJ, "Protein prenyltransferases", J Biol Chem, 271, pp.5289~5292 (1996)
  26. Fisher JE, "Alendronate mechanism of action: inhibition of osteoclastogenesis and bone resorption are mimicked by lovastatin and blocked by geranylgeraniol", Bone, 23, pp.S339~ (1998)
  27. Fisher JE, "Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro", Cell Biology, 96, pp.133~138 (1999)
  28. Plotkin LI, "Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin", J Clin Invest, 104, pp.1363~1374 (1999)
  29. Thunyakitpisal PD, "Simvastatin, an HMG-CoA Reductase Inhibitor, reduced the Expression of Matrix Metalloproteinase-9 (Gelatinase B) in Osteoblastic Cell and HT1080 Fibrosarcoma Cells", J Pharmacol Sci, 94, pp.403~409 (2004)
  30. Fromigué O, "RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42", p44- MAPKs-Bcl signaling independently of BMP-2 and cell differentiation, 2006, pp.13, 1845~1856
  31. Zhong WB, "Lovastatin Induces Apoptosis of Anaplastic Thyroid Cancer Cell via Inhibition of Protein Geranylgeranylation and de novo Protein Synthesis", Endocrinology, 144, pp.3852~3859 (2003)
  32. Cafforio P, "Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells", Carcinogenesis, 26, pp.883~891 (2003)

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