{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:39:39Z","timestamp":1778099979940,"version":"3.51.4"},"reference-count":20,"publisher":"The Company of Biologists","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:p>Despite evidence that DAP12 regulates osteoclasts, mice lacking the ITAM-bearing protein exhibit only mild osteopetrosis. Alternatively, Dap12\u2212\/\u2212 mice, also lacking FcR\u03b3, are severely osteopetrotic, suggesting that FcR\u03b3 compensates for DAP12 deficiency in the bone-resorbing polykaryons. Controversy exists, however, as to whether these co-stimulatory molecules regulate differentiation of osteoclasts or the capacity of the mature cell to degrade bone. We find that Dap12\u2212\/\u2212 osteoclasts differentiate normally when generated on osteoblasts but have a dysfunctional cytoskeleton, impairing their ability to transmigrate through the osteoblast layer and resorb bone. To determine whether the FcR\u03b3 co-receptor, OSCAR mediates osteoclast function in the absence of DAP12, we overexpressed OSCAR fused to FLAG (OSCAR-FLAG), in Dap12\u2212\/\u2212 osteoclasts. OSCAR-FLAG partially rescues the abnormal cytoskeleton of Dap12\u2212\/\u2212 osteoclasts grown on bone, but not those grown on osteoblasts. Thus, cytoskeletal dysfunction, and not arrested differentiation, is the dominant consequence of DAP12 deficiency in osteoclasts. The failure of osteoblasts to normalize Dap12\u2212\/\u2212 osteoclasts indicates that functionally relevant quantities of OSCAR ligand do not reside in bone-forming cells.<\/jats:p>","DOI":"10.1242\/jcs.069872","type":"journal-article","created":{"date-parts":[[2010,8,18]],"date-time":"2010-08-18T18:15:53Z","timestamp":1282155353000},"page":"2955-2963","source":"Crossref","is-referenced-by-count":32,"title":["Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts"],"prefix":"10.1242","volume":"123","author":[{"given":"Wei","family":"Zou","sequence":"first","affiliation":[{"name":"Pathology and Immunology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Pathology and Immunology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa S.","family":"Craft","sequence":"additional","affiliation":[{"name":"Cell Biology and Physiology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Broekelmann","sequence":"additional","affiliation":[{"name":"Cell Biology and Physiology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Mecham","sequence":"additional","affiliation":[{"name":"Cell Biology and Physiology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Teitelbaum","sequence":"additional","affiliation":[{"name":"Pathology and Immunology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042521065860500_R1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nm0504-458","article-title":"Arming the osteoclast","volume":"10","author":"Baron","year":"2004","journal-title":"Nat. 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