Transmigration: A New Property of Mature Multinucleated Osteoclasts
Open accessAbstract
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.
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In osteoclasts, MMP inhibitors did not affect actin organization per se.
“However, in osteoclasts, MMP inhibitors did not affect actin organization per sé,142”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [142]
Inhibition of c-src and subsequent actin organization in osteoclast precursors prevents osteoclasts from migrating through the osteoblast layer.
“The inhibition of c-src and subsequent actin organization in osteoclast precursors prevent osteoclasts from migrating through the osteoblast layer.142”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [142]
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References 56 · Cited by 41
Research works printed but not linked: 2
- Vaananen K, Zhao H 2002 Osteoclast function. In: Bilezikian JP, Raisz LG, Rodan GA (eds.) Principles of Bone Biology. Academic Press, San Diego, CA, USA, pp. 127-139.
- Burkhardt R, Bartl R, Frisch B, Jager K, Mahl C, Hill W, Kettner G 1984 The structural relationship of bone forming and endothelial cells of the bone marrow. In: Arlet J, Ficat RP, Hungerford DS (eds.) Bone Circulation. Williams & Wilkins, Baltimore, MD, USA, pp. 1-49.
- Authors
- Saltel, F., Chabadel, A., Zhao, Y., Lafage-Proust, M.-H., Clézardin, P., Jurdic, P., & Bonnelye, E.
- Affiliations
- École Normale Supérieure de Lyon (FR)
- Inserm (FR)
- Faculté de Médecine, Laboratoire de Biologie du Tissu Osseux, E INSERM 366, Saint-Étienne Cedex 2, France
- Corresponding author
- Jurdic, Pierre
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-01
- Volume
- 21
- Issue
- 12
- Pages
- 1913-1923
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2011390056
- Cited by
- 41
- References
- 56
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- osteoclasts, transmigration, breast cancer bone metastasis, Src kinase, matrix metalloproteinases, bisphosphonates, risedronate, bone microenvironment, bone remodeling, osteoclast resorption, podosomes, actin cytoskeleton
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Dipeptides, Female, Male, Osteoclasts, Protease Inhibitors, Pyrimidines, Giant Cells, Proto-Oncogene Proteins pp60(c-src), Bone Remodeling, Coculture Techniques, Matrix Metalloproteinases, Mice, Matrix Metalloproteinase Inhibitors
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