{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:13:06Z","timestamp":1784887986816,"version":"3.55.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,24]]},"abstract":"<jats:p>\n                    Osteoclasts, cells of myeloid lineage, play a unique role in bone resorption, maintaining skeletal homeostasis in concert with bone-producing osteoblasts. Osteoclast development and maturation (osteoclastogenesis) is driven by receptor activator of NF-\u03baB ligand and macrophage-colony stimulating factor and invariably requires a signal initiated by immunoreceptor tyrosine-based activation motif (ITAM)-harboring Fc receptor common \u03b3 chain or DNAX-activating protein (DAP)12 (also referred to as KARAP or TYROBP) that associates with the cognate immunoreceptors. Here, we show that a third adaptor, YINM costimulatory motif-harboring DAP10, triggers osteoclastogenesis and bone remodeling. DAP10-deficient (\n                    <jats:italic>DAP10<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice become osteopetrotic with age, concomitant with a reduction in osteoclasts. The DAP10-associating receptor was identified as myeloid DAP12-associating lectin-1 (MDL-1), whose physiologic function has not been found. MDL-1-mediated stimulation of osteoclast precursor cells resulted in augmented osteoclastogenesis in vitro. MDL-1 associates with both DAP12 and DAP10 in osteoclasts and bone marrow-derived macrophages, where DAP10 association depends almost entirely on DAP12, suggesting a formation of MDL-1\u2013DAP12\/DAP10 trimolecular complexes harboring ITAM\/YINM stimulatory\/costimulatory motifs within a complex that could be a novel therapeutic target for skeletal and inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900463106","type":"journal-article","created":{"date-parts":[[2009,2,27]],"date-time":"2009-02-27T21:11:49Z","timestamp":1235769109000},"page":"4816-4821","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12"],"prefix":"10.1073","volume":"106","author":[{"given":"Masanori","family":"Inui","sequence":"first","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Asahikawa Medical College, Higashi 2-1-1, Midorigaoka, Asahikawa 078-8510, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Sugahara-Tobinai","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shion","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kumanogoh","sequence":"additional","affiliation":[{"name":"Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00157-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1508"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1122"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00369-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1402.071"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/35642"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.51.34115"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02444"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401602101"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/77153"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16923"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62251-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030027"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011681"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.5261"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021945"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.4991"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28775"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.037"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.730"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.4049\/jimmunol.163.9.4651","article-title":"Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties","volume":"163","author":"Chang C","year":"1999","unstructured":"C Chang, et al., Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. 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