Osteoblast differentiation of NIH3T3 fibroblasts is associated with changes in the IGF-I-IGFBP expression pattern

• Autorzy: Abdallah B M
• Języki publikacji: EN

Abstrakty

EN

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are essential regulators for osteoblast proliferation and differentiation. It has been reported that Dexamethasone (Dex), an active glucocorticoid (GC) analogue, synergizes the stimulatory effect of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on osteoblast differentiation in the mouse fibroblastic cell line NIH3T3. I investigated whether this stimulatory effect is associated with changes in the expression pattern of the IGF/IGFBP system. Quantitative real-time PCR technology was used to quantify the gene expression levels of the IGF-system during osteoblast differentiation and in response to 1,25(OH)(2)D(3) or Dex alone under serum-containing and serum-free culture conditions. Interestingly, NIH3T3 was shown to express high mRNA levels of IGF-I, IGF-II and IGFBP-5, and low levels of both IGFBP-2 and-6. During osteoblast differentiation (days 6-12), IGF-I mRNA was repressed by more than 60%, while the transcript of IGFBP-5 was markedly up-regulated, by more than 50-fold. Similarly, treatment with Dex alone resulted in a dose-and time-dependent increase in the expression of IGFBP-5 and a decrease in IGF-I mRNA. Treatment with 1,25(OH)(2)D(3) alone increased the mRNA levels of IGF-I and IGFBP-6 by around 4-and 7-fold, respectively, in a dose-and time-dependent manner. In conclusion, my data demonstrated that osteoblast differentiation of NIH3T3 is associated with changes in the expression pattern of IGFs/IGFBPs, which are regulated by glucocorticoid in the presence of 1,25(OH)(2)D(3). Modulation of the IGF/IGFBP levels by glucocorticoid might suggest important roles for the IGF-system in mediating the osteoblast differentiation of the NIH3T3 cell line.

Słowa kluczowe

EN

gene expression; bone; fibroblast; insulin-like growth factor; proliferation; cytokine; regulator; polymerase chain reaction; growth factor; binding protein; osteoblast; systemic hormone; differentiation

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2006
• Tom: 11
• Numer: 4
• Opis fizyczny: p.461-474,fig.,ref.

Twórcy

autor

Abdallah B M

• Helwan University, Cairo, Egypt

Bibliografia

• 1. Kassem, M., Kristiansen, M. and Abdallah, B.M. Mesenchymal stem cells: cell biology and potential use in therapy. Basic Clin. Pharmacol. Toxicol. 95 (2004) 209-214.
• 2. Langdahl, B.L., Kassem, M., Moller, M.K. and Eriksen, E.F. The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone. Eur. J. Clin. Invest. 28 (1998) 176-183.
• 3. Rajaram, S., Baylink, D.J. and Mohan, S. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr. Rev. 18 (1997) 801-831.
• 4. Mohan, S. and Baylink, D.J. IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. J. Endocrinol. 175 (2002) 19-31.
• 5. Robson, H., Siebler, T., Shalet, S.M. and Williams, G.R. Interactions between GH, IGF-I, glucocorticoids, and thyroid hormones during skeletal growth. Pediatr. Res. 52 (2002) 137-147.
• 6. Eijken, M., Koedam, M., van Driel, M., Buurman, C.J., Pols, H.A. and van Leeuwen, J.P. The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol. Cell Endocrinol. 248 (2006) 87-93.
• 7. Delany, A.M. and Canalis, E. Transcriptional repression of insulin-like growth factor I by glucocorticoids in rat bone cells. Endocrinology 136 (1995) 4776-4781.
• 8. Cheng, S.L., Zhang, S.F., Mohan, S., Lecanda, F., Fausto, A., Hunt, A.H., Canalis, E. and Avioli, L.V. Regulation of insulin-like growth factors I and II and their binding proteins in human bone marrow stromal cells by dexamethasone. J. Cell. Biochem. 71 (1998) 449-458.
• 9. Gurlek, A., Pittelkow, M.R. and Kumar, R. Modulation of growth factor/cytokine synthesis and signaling by 1alpha,25-dihydroxyvitamin D(3): implications in cell growth and differentiation. Endocr. Rev. 23 (2002) 763-786.
• 10. Kveiborg, M., Flyvbjerg, A., Eriksen, E.F. and Kassem, M. 1,25- Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor-binding proteins-2, -3 and -4 in human bone marrow stromal cells. Eur. J. Endocrinol. 144 (2001) 549-557.
• 11. Nakao, Y., Hilliker, S., Baylink, D.J. and Mohan, S. Studies on the regulation of insulin-like growth factor binding protein 3 secretion in human osteosarcoma cells in vitro. J. Bone Miner. Res. 9 (1994) 865-872.
• 12. Shui, C. and Scutt, A.M. Mouse embryo-derived NIH3T3 fibroblasts adopt an osteoblast-like phenotype when treated with 1alpha,25-dihydroxyvitamin D(3) and dexamethasone in vitro. J. Cell Physiol. 193 (2002) 164-172.
• 13. Wang, E.A., Israel, D.I., Kelly, S. and Luxenberg, D.P. Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. Growth Factors 9 (1993) 57-71.
• 14. Xiao, Z.S., Hinson, T.K. and Quarles, L.D. Cbfa1 isoform overexpression upregulates osteocalcin gene expression in non-osteoblastic and preosteoblastic cells. J. Cell. Biochem. 74 (1999) 596-605.
• 15. Abdallah, B.M., Haack-Sorensen, M., Fink, T. and Kassem, M. Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females. Bone 39 (2006) 181-188.
• 16. Koch, H., Jadlowiec, J.A. and Campbell, P.G. Insulin-like growth factor-I induces early osteoblast gene expression in human mesenchymal stem cells. Stem Cells Dev. 14 (2005) 621-631.
• 17. Barnes, P.J. Corticosteroids: the drugs to beat. Eur. J. Pharmacol. 533 (2006) 2-14.
• 18. Canalis, E., Bilezikian, J.P., Angeli, A. and Giustina, A. Perspectives on glucocorticoid-induced osteoporosis. Bone 34 (2004) 593-598.
• 19. Smith, E., Coetzee, G.A. and Frenkel, B. Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase3beta. J. Biol. Chem. 277 (2002) 18191-18197.
• 20. Jorgensen, N.R., Henriksen, Z., Sorensen, O.H. and Civitelli, R. Dexamethasone, BMP-2and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype: validation of an in vitro model for human bone marrow-derived primary osteoblasts. Steroids 69 (2004) 219-226.
• 21. Minuto, F., Palermo, C., Arvigo, M. and Barreca, A.M. The IGF system and bone. J. Endocrinol. Invest. 28 (2005) 8-10.
• 22. Chen, T.L., Mallory, J.B. and Hintz, R.L. Dexamethasone and 1,25(OH)2 vitamin D3 modulate the synthesis of insulin-like growth factor-I in osteoblast-like cells. Calcif. Tissue Int. 48 (1991) 278-282.
• 23. Chevalley, T., Strong, D.D., Mohan, S., Baylink, D. and Linkhart, T.A. Evidence for a role for insulin-like growth factor binding proteins in glucocorticoid inhibition of normal human osteoblast-like cell proliferation. Eur. J. Endocrinol. 134 (1996) 591-601.
• 24. Conover, C.A., Clarkson, J.T. and Bale, L.K. Effect of glucocorticoid on insulin-like growth factor (IGF) regulation of IGF-binding protein expression in fibroblasts. Endocrinology 136 (1995) 1403-1410.
• 25. Fielder, P.J., Tauber, J.P., Wilson, K.F., Pham, H.M. and Rosenfeld, R.G. Insulin-like growth factors (IGFs) stimulate and dexamethasone inhibits IGF binding protein (BP)-5 expression in a mouse pituitary cell line. Growth Regul. 3 (1993) 226-234.
• 26. Firth, S.M. and Baxter, R.C. Cellular actions of the insulin-like growth factor binding proteins. Endocr. Rev. 23 (2002) 824-854.
• 27. Miyakoshi, N., Richman, C., Kasukawa, Y., Linkhart, T.A., Baylink, D.J. and Mohan, S. Evidence that IGF-binding protein-5 functions as a growth factor. J. Clin. Invest. 107 (2001) 73-81.
• 28. Durant, D., Pereira, R.M. and Canalis, E. Overexpression of insulin-like growth factor binding protein-5 decreases osteoblastic function in vitro. Bone 35 (2004) 1256-1262.
• 29. Jia, D. and Heersche, J.N. Expression of insulin-like growth factor system constituents in differentiating rat osteoblastic cell populations. Growth Horm. IGF. Res. 12 (2002) 399-410.
• 30. Chen, T.L., Chang, L.Y., Bates, R.L. and Perlman, A.J. Dexamethasone and 1,25-dihydroxyvitamin D3 modulation of insulin-like growth factor-binding proteins in rat osteoblast-like cell cultures. Endocrinology 128 (1991) 73-80.
• 31. Chenu, C., Valentin-Opran, A., Chavassieux, P., Saez, S., Meunier, P.J. and Delmas, P.D. Insulin like growth factor I hormonal regulation by growth hormone and by 1,25(OH)2D3 and activity on human osteoblast-like cells in short-term cultures. Bone 11 (1990) 81-86.
• 32. Linkhart, T.A. and Keffer, M.J. Differential regulation of insulin-like growth factor-I (IGF-I) and IGF-II release from cultured neonatal mouse calvaria by parathyroid hormone, transforming growth factor-betaand 1,25- dihydroxyvitamin D3. Endocrinology 128 (1991) 1511-1518.
• 33. Schmid, C., Schlapfer, I., Gosteli-Peter, M.A., Hauri, C., Froesch, E.R. and Zapf, J. 1 alpha,25-dihydroxyvitamin D3 increases IGF binding protein-5 expression in cultured osteoblasts. FEBS Lett. 392 (1996) 21-24.
• 34. Kim, E.J., Schaffer, B.S., Kang, Y.H., Macdonald, R.G. and Park, J.H. Decreased production of insulin-like growth factor-binding protein (IGFBP)-6 by transfection of colon cancer cells with an antisense IGFBP-6 cDNA construct leads to stimulation of cell proliferation. J. Gastroenterol. Hepatol. 17 (2002) 563-570.
• 35. Schmid, C. Insulin-like growth factors. Cell Biol. Int. 19 (1995) 445-457.
• 36. Yan, T., Wergedal, J., Zhou, Y., Mohan, S., Baylink, D.J. and Strong, D.D. Inhibition of human osteoblast marker gene expression by retinoids is mediated in part by insulin-like growth factor binding protein-6. Growth Horm. IGF. Res. 11 (2001) 368-377.
• 37. Bach, L.A. IGFBP-6 five years on; not so 'forgotten'? Growth Horm. IGF. Res. 15 (2005) 185-192.