The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice
Open accessAbstract
Osteoclasts are terminally differentiated leukocytes that erode the mineralized bone matrix. Osteoclastogenesis requires costimulatory receptor signaling through adaptors containing immunoreceptor tyrosine-based activation motifs (ITAMs), such as Fc receptor common γ (FcRγ) and DNAX-activating protein of 12 kDa. Identification of these ITAM-containing receptors and their ligands remains a high research priority, since the stimuli for osteoclastogenesis are only partly defined. Osteoclast-associated receptor (OSCAR) was proposed to be a potent FcRγ-associated costimulatory receptor expressed by preosteoclasts in vitro, but OSCAR lacks a cognate ligand and its role in vivo has been unclear. Using samples from mice and patients deficient in various ITAM signaling pathways, we show here that OSCAR costimulates one of the major FcRγ-associated pathways required for osteoclastogenesis in vivo. Furthermore, we found that OSCAR binds to specific motifs within fibrillar collagens in the ECM that become revealed on nonquiescent bone surfaces in which osteoclasts undergo maturation and terminal differentiation in vivo. OSCAR promoted osteoclastogenesis in vivo, and OSCAR binding to its collagen motif led to signaling that increased numbers of osteoclasts in culture. Thus, our results suggest that ITAM-containing receptors can respond to exposed ligands in collagen, leading to the functional differentiation of leukocytes, which provides what we believe to be a new concept for ITAM regulation of cytokine receptors in different tissue microenvironments.
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Cites
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
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Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts
Paloneva, J., Kestilä, M., Wu, J., Salminen, A., Böhling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B. H., Phillips, J. H., Pekkarinen, P., et al. (2000) · Nature Genetics · doi:10.1038/77153 · Cited by 460
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DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features
Paloneva, J., Mandelin, J., Kiialainen, A., Böhling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., & Peltonen, L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030027 · Cited by 318
The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2
Klünemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000160304.00003.ca · Cited by 254
PLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2
Mao, D., Epple, H., Uthgenannt, B., Novack, D. V., & Faccio, R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28775 · Cited by 214
Essential Role of DAP12 Signaling in Macrophage Programming into a Fusion-Competent State
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Cited by
Regulation of Osteoclast Differentiation by Cytokine Networks
Amarasekara, D. S., Yun, H., Kim, S., Lee, N., Kim, H., & Rho, J. (2018) · Immune Network · doi:10.4110/in.2018.18.e8 · Cited by 518
Self-citationAdvances in the regulation of osteoclasts and osteoclast functions
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New insights into osteoclastogenic signaling mechanisms
Nakashima, T., Hayashi, M., & Takayanagi, H. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.05.005 · Cited by 342
Self-citationJoyce, K., Fabra, G. T., Bozkurt, Y., & Pandit, A. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00512-8 · Cited by 316
The role of cytokines in inflammatory bone loss
Souza, P. P. C., & Lerner, U. H. (2013) · Immunological Investigations · doi:10.3109/08820139.2013.822766 · Cited by 269
Metadata
- Authors
- Barrow, A. D., Raynal, N., Andersen, T. L., Slatter, D. A., Bihan, D., Pugh, N., Cella, M., Kim, T., Rho, J., Negishi-Koga, T., Delaisse, J.-M., Takayanagi, H., Lorenzo, J., Colonna, M., Farndale, R. W., Choi, Y., & Trowsdale, J.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-09-01
- Volume
- 121
- Issue
- 9
- Pages
- 3505-3516
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1994517874
- Cited by
- 207
- References
- 11
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- green
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- Barrow, A. D., Raynal, N., Andersen, T. L., Slatter, D. A., Bihan, D., Pugh, N., Cella, M., Kim, T., Rho, J., Negishi-Koga, T., Delaisse, J.-M., Takayanagi, H., Lorenzo, J., Colonna, M., Farndale, R. W., Choi, Y., & Trowsdale, J. (2011). OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci45913
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