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Specifically, we have identified that in human PBMCs, IL-23 induces the expression of MDL-1, a PU.1 transcriptional target during myeloid differentiation, which orchestrates osteoclast differentiation through activation of DNAX activating protein of 12 kDa and its ITAMs. The molecular events that lead to the differentiation of human macrophages to terminally differentiated osteoclasts are dependent on spleen tyrosine kinase and phospholipase C\u03b32 phosphorylation for the induction of intracellular calcium flux and the subsequent activation of master regulator osteoclast transcription factor NFATc1. IL-23\u2013elicited osteoclastogenesis is independent of the receptor activator of NF-\u03baB ligand pathway and uses a unique myeloid DNAX activating protein of 12 kDa\u2013associated lectin-1+\/DNAX activating protein of 12 kDa+ cell subset. Our data define a novel pathway that is used by IL-23 in myeloid cells and identify a major mechanism for the stimulation of osteoclastogenesis in inflammatory arthritis.<\/jats:p>","DOI":"10.4049\/jimmunol.1401013","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T08:22:58Z","timestamp":1417508578000},"page":"316-324","source":"Crossref","is-referenced-by-count":39,"title":["Crosstalk among IL-23 and DNAX Activating Protein of 12 kDa\u2013Dependent Pathways Promotes Osteoclastogenesis"],"prefix":"10.1093","volume":"194","author":[{"given":"Hyun-Seock","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritu","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Dixit","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California Davis Medical Center , Sacramento, CA 95817"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward P","family":"Bowman","sequence":"additional","affiliation":[{"name":"Discovery Research, Department of Immunology and Immunomodulatory Receptors, Merck Research Laboratories , Palo Alto, CA 94304"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iannis E","family":"Adamopoulos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"},{"name":"Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children\u2013Northern California , Sacramento, CA 95817"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"key":"2025031310004549100_r1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1182\/blood-2007-12-077917","article-title":"The phagocytes: neutrophils and monocytes","volume":"112","author":"Dale","year":"2008","journal-title":"Blood"},{"key":"2025031310004549100_r2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"2025031310004549100_r3","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1182\/blood-2011-09-379214","article-title":"Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling","volume":"119","author":"Hume","year":"2012","journal-title":"Blood"},{"key":"2025031310004549100_r4","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1182\/blood.V88.7.2531.bloodjournal8872531","article-title":"Macrophage colony-stimulating factor induces substantial osteoclast generation and bone resorption in human bone marrow cultures","volume":"88","author":"Sarma","year":"1996","journal-title":"Blood"},{"key":"2025031310004549100_r5","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.1210\/endo.137.9.8756585","article-title":"The human osteoclast precursor circulates in the monocyte fraction","volume":"137","author":"Fujikawa","year":"1996","journal-title":"Endocrinology"},{"key":"2025031310004549100_r6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"2025031310004549100_r7","doi-asserted-by":"crossref","first-page":"6383","DOI":"10.4049\/jimmunol.161.11.6383","article-title":"IL-17 stimulates granulopoiesis in mice: use of an alternate, novel gene therapy-derived method for in vivo evaluation of cytokines","volume":"161","author":"Schwarzenberger","year":"1998","journal-title":"J. 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