{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:26:32Z","timestamp":1790429192653,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T00:00:00Z","timestamp":1417651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010AR064755"],"award-info":[{"award-number":["R01\u2010AR064755"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>\n                    Activating\u2010mutations in NOD\u2010like receptor (NLR) family, pyrin domain\u2010containing 3 (NLRP3) cause neonatal\u2010onset multisystem inflammatory disease. However, the ontogeny of skeletal anomalies in this disorder is poorly understood. Mice globally expressing the D301N mutation in\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    (D303N in human) model the human phenotype, including systemic inflammation and skeletal deformities. To gain insights into the skeletal manifestations, we generated mice in which the expression of D301N\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    (\n                    <jats:italic>\n                      Nlrp3\n                      <jats:sup>D301N<\/jats:sup>\n                    <\/jats:italic>\n                    ) is restricted to myeloid cells. These mice exhibit systemic inflammation and severe osteopenia (~60% lower bone mass) similar to mice globally expressing the knock\u2010in mutation, consistent with the paradigm of innate immune\u2010driven cryopyrinopathies. Because systemic inflammation may indirectly affect bone homeostasis, we engineered mice in which\n                    <jats:italic>\n                      Nlrp3\n                      <jats:sup>D301N<\/jats:sup>\n                    <\/jats:italic>\n                    is expressed specifically in osteoclasts, the cells that resorb bone. These mice also develop ~50% lower bone mass due to increased osteolysis, but there is no systemic inflammation and no change in osteoclast number. Mechanistically, aside from its role in IL\u20101\u03b2 maturation,\n                    <jats:italic>\n                      Nlrp3\n                      <jats:sup>D301N<\/jats:sup>\n                    <\/jats:italic>\n                    expression enhances osteoclast bone resorbing ability through reorganization of actin cytoskeleton while promoting the degradation of poly(ADP\u2010ribose) polymerase 1, an inhibitor of osteoclastogenesis. Thus, NLRP3 inflammasome activation is not restricted to the production of proinflammatory mediators but also leads to cytokine\u2010autonomous responses.\u2014Qu, C., Bonar, S. L., Hickman\u2010Brecks, C. L., Abu\u2010Amer, S., McGeough, M. D., Pe\u00f1a, C. A., Broderick, L., Yang, C., Grimston, S., K., Kading, J., Abu\u2010Amer, Y., Novack, D. V., Hoffman, H. M., Civitelli, R., Mbalaviele, G. NLRP3 mediates osteolysis through inflammation\u2010dependent and \u2010independent mechanisms.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    29, 1269\u20101279 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-264804","type":"journal-article","created":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T00:00:12Z","timestamp":1417737612000},"page":"1269-1279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["NLRP3 mediates osteolysis through inflammation\u2010dependent and \u2010independent mechanisms"],"prefix":"10.1096","volume":"29","author":[{"given":"Chao","family":"Qu","sequence":"first","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri L.","family":"Bonar","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia L.","family":"Hickman\u2010Brecks","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer","family":"Abu\u2010Amer","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"McGeough","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology, and Rheumatology University of California, San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla A.","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology, and Rheumatology University of California, San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Broderick","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology, and Rheumatology University of California, San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Grimston","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Kading","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Abu\u2010Amer","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah V.","family":"Novack","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hal M.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Civitelli","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Mbalaviele","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases Washington University School of Medicine St. Louis Missouri 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