HGNC Approved Gene Symbol: OSCAR
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38) : 19:54,094,668-54,100,803 (from NCBI)
Osteoclasts (OCs) are multinucleated cells that develop from myelomonocytic cells upon interaction with osteoblast factors such as MCSF (CSF1; 120420) and TRANCE (TNFSF11; 602642). OCs are essential for bone resorption and for bone homeostasis. OSCAR is expressed specifically on OC-lineage cells and regulates osteoclastogenesis (Kim et al., 2002).
By PCR subtraction of mouse OC and macrophage cDNA libraries, followed by screening of a human OC cDNA library, Kim et al. (2002) obtained cDNAs encoding mouse and human OSCAR. The deduced 263-amino acid type I transmembrane human protein is 73% identical to the mouse protein. It contains 2 extracellular immunoglobulin-like domains, which are homologous to leukocyte receptor complex proteins (e.g., NKp46; 604530), a charged arg residue in the transmembrane region, and a short cytoplasmic tail. Northern blot analysis detected expression of 1.8- and 1.0-kb transcripts in mouse OCs and bone. No expression was detected in macrophages, dendritic cells, or soft tissues, suggesting specific OC expression. Flow cytometric and immunohistochemical analyses demonstrated expression of mouse Oscar predominantly on mature OCs, with no expression on macrophages, dendritic cells, natural killer cells, or lymphocytes.
Kim et al. (2002) demonstrated that soluble Oscar inhibits the formation of OCs from bone marrow precursor cells stimulated by osteoblasts, but does not inhibit the formation of OCs from myeloid cell lines stimulated with soluble TRANCE. Flow cytometric analysis of osteoblasts suggested the presence of an OSCAR ligand on these cells.
Kim et al. (2005) found that the transcription factor Nfatc1 (600489) induced expression of Oscar by binding directly to specific sites in its promoter region during mouse osteoclast differentiation. Nfatc1, Mitf (156845), and Pu.1 (SPI1; 165170) acted synergistically to stimulate Oscar promoter activity with involvement of the Mkk6 (MAP2K6; 601254)/p38 (MAPK14; 600289) signaling pathway.
Barrow et al. (2015) used a bioinformatics approach to identify collagenous molecules with immunologic roles that contain a putative OSCAR-binding motif. The authors thus identified the collagenous domain of SPD (SFTPD; 178635) and showed that it was a specific, calcium-enhanced binding partner of OSCAR. Full-length SPD in bronchoalveolar lavage fluid also bound OSCAR. Immunofluorescence microscopy demonstrated that SPD-containing alveolar macrophages bound OSCAR in intracellular compartments, whereas OSCAR was predominantly expressed on the surface of interstitial lung and blood CCR2 (601267)-positive inflammatory monocytes. Following stimulation with SPD, these monocytes secreted TNF (191160). OSCAR and SPD were also highly expressed in atherosclerotic plaques in aorta. Barrow et al. (2015) proposed that OSCAR/SPD interaction may be a target in chronic lung inflammatory diseases.
Using BAC clone analysis, Kim et al. (2002) mapped the OSCAR gene to chromosome 19q13.4, within the leukocyte receptor complex. They mapped the mouse gene to chromosome 7 in the PIR region by radiation hybrid analysis.
Barrow, A. D., Palarasah, Y., Bugatti, M., Holehouse, A. S., Byers, D. E., Holtzman, M. J., Vermi, W., Skjodt, K., Crouch, E., Colonna, M. OSCAR is a receptor for surfactant protein D that activates TNF-alpha release from human CCR2+ inflammatory monocytes. J. Immun. 194: 3317-3326, 2015. [PubMed: 25716998] [Full Text: https://doi.org/10.4049/jimmunol.1402289]
Kim, K., Kim, J. H., Lee, J., Jin, H.-M., Lee, S.-H., Fisher, D. E., Kook, H., Kim, K. K., Choi, Y., Kim, N. Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis. J. Biol. Chem. 280: 35209-35216, 2005. [PubMed: 16109714] [Full Text: https://doi.org/10.1074/jbc.M505815200]
Kim, N., Takami, M., Rho, J., Josien, R., Choi, Y. A novel member of the leukocyte receptor complex regulates osteoclast differentiation. J. Exp. Med. 195: 201-209, 2002. [PubMed: 11805147] [Full Text: https://doi.org/10.1084/jem.20011681]