These authors contributed equally to this work.
Transmigration: A New Property of Mature Multinucleated Osteoclasts†
Article first published online: 5 SEP 2006
Copyright © 2006 ASBMR
Journal of Bone and Mineral Research
Volume 21, Issue 12, pages 1913–1923, December 2006
How to Cite
Saltel, F., Chabadel, A., Zhao, Y., Lafage-Proust, M.-H., Clézardin, P., Jurdic, P. and Bonnelye, E. (2006), Transmigration: A New Property of Mature Multinucleated Osteoclasts. J Bone Miner Res, 21: 1913–1923. doi: 10.1359/jbmr.060821
The authors state that they have no conflicts of interest.
- Issue published online: 4 DEC 2009
- Article first published online: 5 SEP 2006
- Manuscript Accepted: 31 AUG 2006
- Manuscript Revised: 12 JUL 2006
- Manuscript Received: 14 APR 2006
- matrix metalloproteinase;
Even though it is assumed that multinucleated osteoclasts are migrating cells on the bone surface to be resorbed, we show that they can also selectively transmigrate through layers of cells usually found in the bone microenvironment. This activity is associated with c-src and MMPs and can be stimulated by bone metastatic breast cancer cells, a process blocked by bisphosphonate treatment.
Introduction: Osteoclasts have an hematopoietic origin and are bone-resorbing cells. Monocytic precursors migrate to the bone surface where they fuse to form multinucleated osteoclasts able to migrate over the bone surface. We studied whether multinucleated osteoclasts were also able to transmigrate through tissues.
Materials and Methods: Murine spleen-derived and green fluorescent protein (GFP)-Raw derived osteoclasts were seeded on osteoblasts and several other cell types. The cells were fixed for 20 minutes, 4 or 12 h after osteoclast seeding, and stained with phalloidin to visualize actin using confocal microscopy. Drugs such as PP2 and GM6001, inhibitors of c-src and matrix metalloproteinases (MMPs), respectively, and risedronate were used to determine osteoclast transmigration regulating factors.
Results: We observed by confocal microscopy that multinucleated osteoclasts specifically transmigrate through confluent layers of various cell types present in the bone microenvironment in vitro. This is an efficient process associated with c-src and MMPs but is independent of podosomes. Moreover, conditioned medium from bone metastatic breast cancer cells stimulates osteoclast transmigration in vitro, a process inhibited by bisphosphonate treatment.
Conclusions: Our data describe a new property of mature multinucleated osteoclasts to transmigrate through various cell types. The ability to control this highly regulated osteoclast transmigration process may offer new therapeutic strategies for bone diseases associated with an imbalance in bone remodeling caused by excessive osteoclast resorption.