The copyright line in this article was changed on August 26, 2014 after original online publication.
CD99 Drives Terminal Differentiation of Osteosarcoma Cells by Acting as a Spatial Regulator of ERK 1/2†
Article first published online: 22 APR 2014
© 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Journal of Bone and Mineral Research
Volume 29, Issue 5, pages 1295–1309, May 2014
How to Cite
Sciandra, M., Marino, M. T., Manara, M. C., Guerzoni, C., Grano, M., Oranger, A., Lucarelli, E., Lollini, P.-L., Dozza, B., Pratelli, L., Di Renzo, M. F., Colombo, M. P., Picci, P. and Scotlandi, K. (2014), CD99 Drives Terminal Differentiation of Osteosarcoma Cells by Acting as a Spatial Regulator of ERK 1/2. J Bone Miner Res, 29: 1295–1309. doi: 10.1002/jbmr.2141
- Issue published online: 22 APR 2014
- Article first published online: 22 APR 2014
- Accepted manuscript online: 6 NOV 2013 02:08AM EST
- Manuscript Accepted: 1 NOV 2013
- Manuscript Revised: 28 OCT 2013
- Manuscript Received: 28 FEB 2013
- AIRC IG10452 to KS
- Italian Ministry of Health MinSAL 1628-2010
- OSTEOBLAST DIFFERENTIATION;
- MAPK SIGNALING;
Differentiation therapy is an attractive treatment for osteosarcoma (OS). CD99 is a cell surface molecule expressed in mesenchymal stem cells and osteoblasts that is maintained during osteoblast differentiation while lost in OS. Herein, we show that whenever OS cells regain CD99, they become prone to reactivate the terminal differentiation program. In differentiating conditions, CD99-transfected OS cells express osteocyte markers, halt proliferation, and largely die by apoptosis, resembling the fate of mature osteoblasts. CD99 induces ERK activation, increasing its membrane-bound/cytoplasmic form rather than affecting its nuclear localization. Through cytoplasmic ERK, CD99 promotes activity of the main osteogenic transcriptional factors AP1 and RUNX2, which in turn enhance osteocalcin and p21WAF1/CIP1, leading to G0/G1 arrest. These data underscore the alternative positions of active ERK into distinct subcellular compartments as key events for determining OS fate. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.