Rat osteoclasts adhere to a wide range of rgd (arg-gly-asp) peptide-containing proteins, including the bone sialoproteins and fibronectin, via a β3 integrin
Abstract
The ligand binding ability of rat osteoclast adhesion receptors was investigated in an attachment assay using osteoclasts disaggregated from bone. Osteoclasts adhered well to the Arg-Gly-Asp (RGD)-containing proteins osteopontin (bone sialoprotein I) and BSP (bone sialoprotein II), vitronectin, fibrinogen, von Willebrand factor, and fibronectin. Osteoclasts also adhered, but less strongly, to type I collagen. No attachment of osteoclasts was observed to thrombospondin, tenascin, laminin, or a range of non-RGD-containing bone proteins and proteins from other sources. The attachment of osteoclasts to all ligands was abolished in the presence of GRGDSP peptide, indicating the involvement of the RGD cell binding sequence in ligand binding. Attachment of osteoclasts to all substrates, with the exception of type I collagen, was also strongly inhibited by the addition of monoclonal antibody F11 to the β3 integrin subunit, indicating that a β3 integrin, probably the vitronectin receptor, was involved. Attachment to type I collagen was blocked by EDTA chelation of divalent cations and was not significantly affected by anti-β3 or anti-β1 antibodies; when taken with the inhibition by RGD peptide, this suggests the involvement of various receptors, possibly including nonintegrin collagen receptors, in the binding of osteoclasts to this protein. These results define the wide range of ligands for extracellular matrix receptors in osteoclasts in vitro. It remains to be established which of these proteins are important in osteoclast adhesion and osteoclastic bone resorption in vivo.
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During bone resorption osteoclasts express αvβ3 and α2β1 integrins to interact with the extracellular matrix, in which the former bind to bone-enriched RGD-containing proteins such as bone sialoprotein and osteopontin, whereas β1 integrins bind to collagen fibrils.
“Thus, during bone resorption osteoclasts express α v β 3 and α 2 β 1 integrins to interact with the extracellular matrix, in which the former bind to bone-enriched RGD-containing proteins, such as bone sialoprotein and osteopontin, whereas β 1 integrins bind to collagen fibrils [133, 134].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [133]
Interaction with the matrix is mediated by the integrin complex α5β3, which recognizes RGD motifs in proteins such as fibronectin, osteopontin and bone sialoprotein.
“The interaction with the matrix is mediated by the integrin complex α5β3, which recognizes RGD motifs in proteins such as fibronectin,190 osteopontin (OPN)191 and bone sialoprotein.192”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [190]
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- Authors
- Helfrich, M. H., Nesbitt, S. A., Dorey, E. L., & Horton, M. A.
- Affiliations
- St Bartholomew's Hospital (GB)
- Corresponding author
- Helfrich, Miep H.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1992-03-01
- Volume
- 7
- Issue
- 3
- Pages
- 335-343
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2054851376
- Cited by
- 214
- References
- 55
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2020: 1 · 2019: 5 · 2018: 1 · 2017: 2 · 2015: 3 · 2013: 5 · 2012: 3
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- closed
- 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)
- Funders
- Imperial Cancer Research Fund
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- osteoclasts, cell adhesion, RGD peptide, CD61, integrin αvβ3, osteopontin, bone sialoprotein, fibronectin, extracellular matrix receptors, type I collagen, ligand binding, bone resorption, integrin antibodies
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Antibodies, Monoclonal, Cell Adhesion, Collagen, Fibronectins, Molecular Sequence Data, Oligopeptides, Osteoclasts, Proteins, Rats, Inbred Strains, Sialoglycoproteins, Integrins, Extracellular Matrix Proteins, Integrin beta3, Rats
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