Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption
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We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express beta 1 and beta 3 integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by alpha v beta 3, while a beta 1 integrin is responsible for attachment to fibronectin. Both the rapid attachment by osteoclasts to intact bone particles and their subsequent resorption are blocked by a monoclonal antibody directed to the alpha v beta 3 complex but not by an antibody against beta 1 integrins. Attachment of osteoclasts to bone is also inhibited with soluble osteopontin, Arg-Gly-Asp-containing peptides derived from both osteopontin and bone sialoprotein, or a monospecific polyclonal antibody against osteopontin. We conclude that both osteoclast adherence to bone and subsequent resorption of its matrix are dependent on interactions between the bone matrix proteins osteopontin and/or bone sialoprotein and the integrin alpha v beta 3. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone.
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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 [192]
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- Authors
- Ross, F. P., Chappel, J., Alvarez, J. I., Sander, D., Butler, W. T., Farach-Carson, M. C., Mintz, K. A., Robey, P. G., Teitelbaum, S. L., & Cheresh, D. A.
- Affiliations
- National Institutes of Health (US)
- Scripps Research Institute (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1993-05
- Volume
- 268
- Issue
- 13
- Pages
- 9901-9907
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1511542029
- Cited by
- 537
- References
- 56
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 11 · 2015: 8 · 2014: 9 · 2013: 15 · 2012: 11
- FWCI
- 28.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar039273-12)
- National Cancer Institute (CA-50286, CA-47526)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR39273)
- Topics
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- osteoclasts, osteopontin, bone sialoprotein, alpha v beta 3 integrin, beta1 integrin, bone resorption, bone matrix proteins, fibronectin, RGD peptide, collagen
- MeSH terms
- Amino Acid Sequence, Animals, Bone Matrix, Bone Resorption, Cell Adhesion, Humans, Kinetics, Models, Biological, Molecular Sequence Data, Oligopeptides, Osteoclasts, Sialoglycoproteins, Integrins, Rats, Osteopontin, Integrin-Binding Sialoprotein
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