Statin-induced calcification in human mesenchymal stem cells is cell death related

Journal of Cellular and Molecular Medicine

Volumn 13, Issue 11-12, 2009, Pages 4465-4473

  Kupcsik, Laszlo ^a,b   Meurya, Thomas ^a,c   Flury, Matthias ^d   Stoddart, Martin ^a   Alini, Mauro ^a  

^a AO RESEARCH INSTITUTE   (Switzerland)

^b EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^c SHRINERS HOSPITAL FOR CHILDREN   (Canada)

^d SCHULTHESS CLINIC   (Switzerland)

Author keywords

Adult bone marrow stem cells; Differentiation; Hydroxymethylglutaryl CoA reductase inhibitors; Mesenchymal stem cells; Toxicity

Indexed keywords

ALKALINE PHOSPHATASE; BMP2 PROTEIN, HUMAN; BONE MORPHOGENETIC PROTEIN 2; CALCIUM; DNA; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MESSENGER RNA;

ARTICLE; BIOASSAY; BONE MINERALIZATION; CELL COUNT; CELL DEATH; CELL SURVIVAL; DRUG EFFECT; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETICS; HUMAN; MESENCHYMAL STEM CELL; METABOLISM; STAINING;

ALKALINE PHOSPHATASE; BIOLOGICAL ASSAY; BONE MORPHOGENETIC PROTEIN 2; CALCIFICATION, PHYSIOLOGIC; CALCIUM; CELL COUNT; CELL DEATH; CELL SURVIVAL; DNA; GENE EXPRESSION REGULATION; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MESENCHYMAL STEM CELLS; RNA, MESSENGER; STAINING AND LABELING;

RATTUS;

EID: 77951162086     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1582-4934.2008.00545.x     Document Type: Article

References (36)

1. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990, 343:425-30.
2. Ghosh PM, Mott GE, Ghosh-Choudhury N. Lovastatin induces apoptosis by inhibiting mitotic and post-mitotic events in cultured mesangial cells. Biochim Biophys Acta. 1997, 1359:13-24.
3. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001, 21:1712-9.
4. Quesney-Huneeus V, Wiley MH, Siperstein MD. Essential role for mevalonate synthesis in DNA replication. Proc Natl Acad Sci USA. 1979, 76:5056-60.
5. Mundy G, Garrett R, Harris S. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999, 286:1946-9.
6. Chan KA, Andrade SE, Boles M. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet. 2000, 355:2185-8.
7. Solomon DH, Finkelstein JS, Wang PS. Statin lipid-lowering drugs and bone mineral density. Pharmacoepidemiol Drug Saf. 2005, 14:219-26.
8. Pasco JA, Kotowicz MA, Henry MJ. Statin use, bone mineral density, and fracture risk: Geelong Osteoporosis Study. Arch Intern Med. 2002, 162:537-40.
9. Rejnmark L, Buus NH, Vestergaard P. Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women. J Bone Miner Res. 2004, 19:737-44.
10. Wada Y, Nakamura Y, Koshiyama H. Lack of positive correlation between statin use and bone mineral density in Japanese subjects with type 2 diabetes. Arch Intern Med. 2000, 160:2865.
11. van Staa TP, Wegman S, de Vries F. Use of statins and risk of fractures. JAMA. 2001, 285:1850-5.
12. Staal A, Frith JC, French MH. The ability of statins to inhibit bone resorption is directly related to their inhibitory effect on HMG-CoA reductase activity. J Bone Miner Res. 2003, 18:88-96.
13. Hughes A, Rogers MJ, Idris AI. A comparison between the effects of hydrophobic and hydrophilic statins on osteoclast function in vitro and ovariectomy-induced bone loss in vivo. Calcif Tissue Int. 2007, 81:403-13.
14. Maeda T, Matsunuma A, Kurahashi I. Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem. 2004, 92:458-71.
15. Ohnaka K, Shimoda S, Nawata H. Pitavastatin enhanced BMP-2 and osteocalcin expression by inhibition of Rho-associated kinase in human osteoblasts. Biochem Biophys Res Commun. 2001, 287:337-42.
16. Maeda T, Matsunuma A, Kawane T. Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun. 2001, 280:874-7.
17. Li X, Cui Q, Kao C. Lovastatin inhibits adipogenic and stimulates osteogenic differentiation by suppressing PPARgamma2 and increasing Cbfa1/Runx2 expression in bone marrow mesenchymal cell cultures. Bone. 2003, 33:652-9.
18. Benoit DSW, Nuttelman CR, Collins SD. Synthesis and characterization of a fluvastatin-releasing hydrogel delivery system to modulate hMSC differentiation and function for bone regeneration. Biomaterials. 2006, 27:6102-10.
19. Baek KH, Lee WY, Oh KW. The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells. J Korean Med Sci. 2005, 20:438-44.
20. Lee OK-S, Ko YC, Kuo TK. Fluvastatin and lovastatin but not pravastatin induce neuroglial differentiation in human mesenchymal stem cells. J Cell Biochem. 2004, 93:917-28.
21. Song C, Guo Z, Ma Q. Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochem Biophys Res Commun. 2003, 308:458-62.
22. Sonobe M, Hattori K, Tomita N. Stimulatory effects of statins on bone marrow-derived mesenchymal stem cells. Study of a new therapeutic agent for fracture. Biomed Mater Eng. 2005, 15:261-7.
23. Martin I, Muraglia A, Campanile G. Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow. Endocrinology. 1997, 138:4456-62.
24. Walsh S, Jefferiss C, Stewart K. Expression of the developmental markers STRO-1 and alkaline phosphatase in cultures of human marrow stromal cells: regulation by fibroblast growth factor (FGF)-2 and relationship to the expression of FGF receptors 1-4. Bone. 2000, 27:185-95.
25. Bianchi G, Banfi A, Mastrogiacomo M. Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Exp Cell Res. 2003, 287:98-105.
26. Labarca C, Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980, 102:344-52.
27. Alini M, Carey D, Hirata S. Cellular and matrix changes before and at the time of calcification in the growth plate studied in vitro: arrest of type X collagen synthesis and net loss of collagen when calcification is initiated. J Bone Miner Res. 1994, 9:1077-87.
28. Meury T, Verrier S, Alini M. Human endothelial cells inhibit BMSC differentiation into mature osteoblasts in vitro by interfering with osterix expression. J Cell Biochem. 2006, 98:992-1006.
29. R: A language and environment for statistical computing 2005, R. Development Core Team, Vienna, Austria, R Foundation for Statistical Computing
30. Sugawara Y, Suzuki K, Koshikawa M. Necessity of enzymatic activity of alkaline phosphatase for mineralization of osteoblastic cells. Jpn J Pharmacol. 2002, 88:262-9.
31. Nakai D, Nakagomi R, Furuta Y. Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes. J Pharmacol Exp Ther. 2001, 297:861-7.
32. Aubin JE, Triffitt JT. Mesenchymal stem cells and osteoblast differentiation. Principles of bone biology 2002, 59-81. Bilezikian JP, Raisz LGRodan GA. In, editors, San Diego, CA, Academic Press, pp
33. Zimmermann B, Wachtel HC, Noppe C. Patterns of mineralization in vitro. Cell Tissue Res. 1991, 263:483-93.
34. Ura H, Obara T, Nishino N. Cytotoxicity of simvastatin to pancreatic adenocarcinoma cells containing mutant ras gene. Jpn J Cancer Res. 1994, 85:633-8.
35. Vamvakopoulos JE, Green C. HMG-CoA reductase inhibition aborts functional differentiation and triggers apoptosis in cultured primary human monocytes: a potential mechanism of statin-mediated vasculoprotection. BMC Cardiovasc Disord. 2003, 3:6.
36. Xu R, Chen J, Cong X. Lovastatin protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis by activation of PI3K/Akt and ERK1/2. J Cell Biochem. 2008, 103:256-69.