The Architecture of the Adhesive Apparatus of Cultured Osteoclasts: From Podosome Formation to Sealing Zone Assembly
Open accessAbstract
BACKGROUND: Osteoclasts are bone-degrading cells, which play a central role in physiological bone remodeling. Unbalanced osteoclast activity is largely responsible for pathological conditions such as osteoporosis. Osteoclasts develop specialized adhesion structures, the so-called podosomes, which subsequently undergo dramatic reorganization into sealing zones. These ring-like adhesion structures, which delimit the resorption site, effectively seal the cell to the substrate forming a diffusion barrier. The structural integrity of the sealing zone is essential for the cell ability to degrade bone, yet its structural organization is poorly understood. PRINCIPAL FINDINGS: Combining high-resolution scanning electron microscopy with fluorescence microscopy performed on the same sample, we mapped the molecular architecture of the osteoclast resorptive apparatus from individual podosomes to the sealing zone, at an unprecedented resolution. Podosomes are composed of an actin-bundle core, flanked by a ring containing adhesion proteins connected to the core via dome-like radial actin fibers. The sealing zone, hallmark of bone-resorbing osteoclasts, consists of a dense array of podosomes communicating through a network of actin filaments, parallel to the substrate and anchored to the adhesive plaque domain via radial actin fibers. SIGNIFICANCE: The sealing zone of osteoclasts cultured on bone is made of structural units clearly related to individual podosomes. It differs from individual or clustered podosomes in the higher density and degree of inter-connectivity of its building blocks, thus forming a unique continuous functional structure connecting the cell to its extracellular milieu. Through this continuous structure, signals reporting on the substrate condition may be transmitted to the whole cell, modulating the cell response under physiological and pathological conditions.
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These osteoclast membrane domains are only formed when osteoclasts are in contact with extracellular mineralized matrix, in a process in which αvβ3-integrin and CD44 mediate the attachment of osteoclast podosomes to the bone surface.
“It is important to mention that these domains are only formed when osteoclasts are in contact with extracellular mineralized matrix, in a process which α v β 3-integrin, as well as the CD44, mediates the attachment of the osteoclast podosomes to the bone surface [96–99].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [98]
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Retracted
- Authors
- Luxenburg, C., Geblinger, D., Klein, E., Anderson, K., Hanein, D., Geiger, B., & Addadi, L.
- Affiliations
- Weizmann Institute of Science (IL)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Addadi, Lia
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-01-31
- Volume
- 2
- Issue
- 1
- Pages
- e179
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC1779809
- OpenAlex
- W2026266643
- Cited by
- 285
- References
- 39
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 25 · 2019: 20 · 2018: 17 · 2017: 14 · 2016: 19 · 2015: 19 · 2014: 21 · 2013: 19 · 2012: 17
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5u54gm064346-10, GM-64346, U54 GM64346)
- National Institute of General Medical Sciences (U54-GM064346, GM-64346, U54 GM 64346)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- osteoclasts, podosomes, sealing zone, bone resorption, actin cytoskeleton, cell-substrate adhesion, bone remodeling, osteoporosis
- MeSH terms
- Actins, Animals, Cell Adhesion, Cells, Cultured, Cytoskeleton, Immunohistochemistry, Microscopy, Electron, Scanning, Osteoclasts, Recombinant Fusion Proteins, Cell Surface Extensions, Mice, Paxillin
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