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Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies

  1. M Silvina Molinuevo,
  2. Leon Schurman,
  3. Antonio D McCarthy,
  4. Ana M Cortizo,
  5. María J Tolosa,
  6. M Virginia Gangoiti,
  7. Veronica Arnol,
  8. Claudia Sedlinsky*

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.090732

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 2, pages 211–221, February 2010

Additional Information

How to Cite

Molinuevo, M. S., Schurman, L., McCarthy, A. D., Cortizo, A. M., Tolosa, M. J., Gangoiti, M. V., Arnol, V. and Sedlinsky, C. (2010), Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies. J Bone Miner Res, 25: 211–221. doi: 10.1359/jbmr.090732

Author Information

  1. Grupo de Investigación en Osteopatías y Metabolismo Mineral (GIOMM), Department of Biological Sciences, School of Exact Sciences, National University of La Plata, La Plata, Argentina

*GIOMM, Facultad de Ciencias Exactas, 47 y 115, 1900, La Plata, Provincia, De Buenos Aires, Argentina.

Publication History

  1. Issue published online: 19 FEB 2010
  2. Article first published online: 14 DEC 2009
  3. Manuscript Accepted: 8 JUL 2009
  4. Manuscript Revised: 20 JUN 2009
  5. Manuscript Received: 28 JAN 2009

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References

  • 1
    Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia. 2005; 48: 1292–1299.
  • 2
    Carnevale V, Romagnoli E, D'Erasmo E. Skeletal involvement in patients with diabetes mellitus. Diabetes Metab Res Rev. 2004; 20: 196–204.
  • 3
    Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM. Bone loss and bone turnover in diabetes. Diabetes, 1995; 44: 775–782.
  • 4
    Yamagishi S, Nakamura K, Inoue H. Possible participation of advanced glycation end- products in the pathogenesis of osteoporosis in diabetic patients. Med Hypotheses. 2005; 65: 1013–1015.
  • 5
    Vlassara H, Palace MR. Diabetes and advanced glycation end-products. J Intern Med. 2002; 251: 87–101.
  • 6
    Gin H, Rigalleau V. Oral anti diabetic polychemotherapy in type 2 diabetes mellitus. Diabetes Metab. 2002; 28: 350–353.
  • 7
    Lecka-Czernik B, Gubrij I, Moerman EJ, et al., Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARγ2. J Cell Biochem. 7 1999; 4: 357–371.
  • 8
    Rzonca SO, Suva LJ, Gaddy D, Montague DC, Lecka-Czernik B. Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology. 2004; 145: 401–406.
  • 9
    Lecka-Czernik B, Moerman EJ, Grant DF, Lehmann JM, Manolagas SC, Jilka RL. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology. 2002; 143: 2376–2384.
  • 10
    Gimble JM, Robinson CE, Wu X, Kelly KA. The function of adipocytes in the bone marrow stroma: an update. Bone. 1996; 19: 421–428.
  • 11
    Lazarenko OP, Rzonca SO, Suva LJ, Lecka-Czernik B. Netoglitazone is a PPAR-γ ligand with selective effects on bone and fat. Bone. 2006; 38: 74–84.
  • 12
    Cortizo AM, Sedlinsky C, McCarthy AD, Blanco A, Schurman L. Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture. Eur J Pharmacol. 2006; 536: 38–46.
  • 13
    Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T. Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun. 2008; 75: 414–419.
  • 14
    Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003; 423: 349–355.
  • 15
    Nuttall ME, Gimble JM. Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol. 2004; 4: 290–294.
  • 16
    Tropel P, Noël D, Platet N, Legrand P, Benabid AL, Berger F. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res. 2004; 295: 395–406.
  • 17
    Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284: 143–147.
  • 18
    Akune T, Ohba S, Kamekura S, et al. PPAR-γ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest. 2004; 113: 846–855.
  • 19
    Guidelines on the handling and training of laboratory animals. In: The Biological Council of Animal Research and Welfare Panel. Potters Bar, England: Universities Federation for Animal Welfare (UFAW), 1992. 1992.
  • 20
    El-Batran SA, Abdel-Salam OME, Nofal SM, Baiuomy AR. Effect of rosiglitazone and nateglinide on serum glucose and lipid profile alone or in combination with the biguanide metformin in diabetic rats. Pharmacol Res. 2006; 53: 69–74.
  • 21
    Santana RB, Xu L, Chase HB, Amar S, Graves DT, Trackman PC. A role for advanced glycation end products in diminished bone healing in type 1 diabetes. Diabetes. 2003; 52: 1502–1510.
  • 22
    Schell H, Lienau J, Epari DR, et al. Osteoclastic activity begins early and increases over the course of bone healing. Bone. 2006; 38: 547–554.
  • 23
    Cortizo AM, Etcheverry SB. Vanadium derivatives act as growth factor-mimetic compounds upon differentiation and proliferation of osteoblast-like UMR106 cells. Mol Cell Biochem. 1995; 145: 97–102.
  • 24
    Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248–254.
  • 25
    Tullberg-Reinert H, Jundt G. In situ measurement of collagen synthesis by human bone cells with a Sirius red-based colorimetric microassay: effects of transforming growth factor β2 and ascorbic acid 2-phosphate. Histochem Cell Biol. 1999; 112: 271–276.
  • 26
    Ueno A, Kitase Y, Moriyama K, Inoue H. MC3T3-E1-conditioned medium-induced mineralization by clonal rat dental pulp cells. Matrix Biol. 2001; 20: 347–355.
  • 27
    Laemmli UK. Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature. 1970; 227: 680–685.
  • 28
    Mercer N, Ahmed H, McCarthy AD, Etcheverry SB, Vasta GR, Cortizo AM. AGE-R3/galectin-3 expression in osteoblast-like cells: regulation by AGEs. Mol Cell Biochem. 2004; 266: 17–24.
  • 29
    Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996; 334: 574–579.
  • 30
    Schindeler A, McDonald MM, Bokko P, Little DG. Bone remodeling during fracture repair: the cellular picture. Semin Cell Dev Biol. 2008; 19: 459–466.
  • 31
    Kume S, Kato S, Yamagishi S, et al. Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone. J Bone Miner Res. 2005; 20: 1647–1658.
  • 32
    Siggelkow H, Rebenstorff K, Kurre W, et al. Development of the osteoblast phenotype in primary human osteoblasts in culture: comparison with rat calvarial cells in osteoblast differentiation. J Cell Biochem. 1999; 75: 22–35.
  • 33
    Quarles LD, Yohay DA, Lever LW, Caton R, Wenstrup RJ. Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J Bone Miner Res. 1992; 7: 683–692.
  • 34
    Horowitz MC, Xi Y, Wilson K, Kacena MA. Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev. 2001; 12: 9–18.
  • 35
    Kahn SE, Zinman B, Lachin JM, et al. Rosiglitazone-associated fractures in type 2 diabetes: an analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care. 2008; 31: 845–851.
  • 36
    Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR. Use of thiazolidinediones and fracture risk. Arch Intern Med. 2008; 168: 820–825.
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