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Transmigration: A New Property of Mature Multinucleated Osteoclasts
Author(s) -
Saltel Frédéric,
Chabadel Anne,
Zhao Yingshe,
LafageProust MarieHélène,
Clézardin Philippe,
Jurdic Pierre,
Bonnelye Edith
Publication year - 2006
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.060821
Subject(s) - osteoclast , podosome , multinucleate , microbiology and biotechnology , giant cell , matrix metalloproteinase , bisphosphonate , bone marrow , chemistry , bone cell , cell , pathology , in vitro , biology , immunology , cytoskeleton , osteoporosis , biochemistry , medicine
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.