RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells

  • Authors:
    • Yohann Wittrant
    • François Lamoureux
    • Kanji Mori
    • Anne Riet
    • Akira Kamijo
    • Dominique Heymann
    • Françoise Redini
  • View Affiliations

  • Published online on: January 1, 2006     https://doi.org/10.3892/ijo.28.1.261
  • Pages: 261-269
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The POS-1 murine model of osteolytic osteosarcoma was used to elucidate the molecular and cellular mechanisms involved in the development of primary bone tumors and associated lung metastasis. The POS-1 cell line is derived from an osteosarcoma tumor which develops spontaneously in C3H mice. The POS-1 cell line was characterized in vitro by mineralization capacity and expression of bone markers by semi-quantitative RT-PCR, compared to primary osteoblasts and bone marrow cells. POS-1 cells showed no mineralization capacity and exhibited an undifferentiated phenotype, expressing both osteoblastic and unexpected osteoclastic markers (TRAP, cathepsin K and RANK). Thereby, experiments were performed to determine whether RANK was functional, by studying the biological activity of murine RANKL through the receptor RANK expressed on POS-1 cells. Results revealed a RANKL-induced increase in ERK phosphorylation, as well as BMP-2 induction at the mRNA and protein levels, and a decrease of POS-1 cell proliferation in the presence of 10 ng/ml RANKL. BMP-2 induction is dependent on the ERK 1/2 signal transduction pathway, as its expression is abolished in the presence of UO126, a specific synthetic inhibitor of the ERK 1/2 pathway. Moreover, a 2-fold molar excess of soluble RANK blocks the RANKL-induced BMP-2 expression, demonstrating that the biological effects of RANKL observed in POS-1 cells are mediated by RANK. This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL.

Related Articles

Journal Cover

January 2006
Volume 28 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Wittrant Y, Lamoureux F, Mori K, Riet A, Kamijo A, Heymann D and Redini F: RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells. Int J Oncol 28: 261-269, 2006
APA
Wittrant, Y., Lamoureux, F., Mori, K., Riet, A., Kamijo, A., Heymann, D., & Redini, F. (2006). RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells. International Journal of Oncology, 28, 261-269. https://doi.org/10.3892/ijo.28.1.261
MLA
Wittrant, Y., Lamoureux, F., Mori, K., Riet, A., Kamijo, A., Heymann, D., Redini, F."RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells". International Journal of Oncology 28.1 (2006): 261-269.
Chicago
Wittrant, Y., Lamoureux, F., Mori, K., Riet, A., Kamijo, A., Heymann, D., Redini, F."RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells". International Journal of Oncology 28, no. 1 (2006): 261-269. https://doi.org/10.3892/ijo.28.1.261