{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:54:58Z","timestamp":1791291298483,"version":"4.3.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,9,26]]},"abstract":"<jats:p>Tumor necrosis factor-related, activation-induced cytokine (TRANCE), a tumor necrosis factor family member, mediates survival of dendritic cells in the immune system and is required for osteoclast differentiation and activation in the skeleton. We report the skeletal phenotype of TRANCE-deficient mice and its rescue by the TRANCE transgene specifically expressed in lymphocytes. TRANCE-deficient mice showed severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibited profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae. These mice had marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes. Transgenic overexpression of TRANCE in lymphocytes of TRANCE-deficient mice rescued osteoclast development in two locations in growing long bones: excavation of marrow cavities permitting hematopoiesis in the marrow spaces, and remodeling of osteopetrotic woven bone in the shafts of long bones into histologically normal lamellar bone. However, osteoclasts in these mice failed to appear at the chondroosseous junction and the metaphyseal periosteum of long bones, nor were they present in tooth eruption pathways. These defects resulted in sclerotic metaphyses with persistence of club-shaped long bones and unerupted teeth, and the growth plate defects were largely unimproved by the TRANCE transgene. Thus, TRANCE-mediated regulation of the skeleton is complex, and impacts chondrocyte differentiation and osteoclast formation in a manner that likely requires local delivery of TRANCE.<\/jats:p>","DOI":"10.1073\/pnas.200294797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"10905-10910","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":252,"title":["Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene"],"prefix":"10.1073","volume":"97","author":[{"given":"Nacksung","family":"Kim","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655; and Howard Hughes Medical Institute, Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Odgren","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655; and Howard Hughes Medical Institute, Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Ku","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655; and Howard Hughes Medical Institute, Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Sandy C.","family":"Marks","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655; and Howard Hughes Medical Institute, Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwon","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655; and Howard Hughes Medical Institute, Laboratory of Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,9,12]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"145","volume-title":"The Vertebrate Body","author":"Romer A S","year":"1962","unstructured":"A S Romer The Vertebrate Body (Saunders, Philadelphia), pp. 145\u2013155 (1962)."},{"key":"e_1_3_3_2_2","first-page":"57","volume-title":"Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism","author":"Broadus A E","year":"1996","unstructured":"A E Broadus Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, ed M Favus (Lippincott-Raven, Philadelphia), pp. 57\u201363 (1996)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001830102"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.12.2075"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.40.25190"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/36593"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/16852"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80232-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90140-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.4049\/jimmunol.162.5.2562","volume":"162","author":"Josien R","year":"1999","unstructured":"R Josien, B R Wong, H L Li, R M Steinman, Y Choi J Immunol 162, 2562\u20132568 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001830206"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(94)90321-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(94)90083-3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00149-0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-6009(90)90086-U"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001460308"},{"key":"e_1_3_3_18_2","first-page":"2","volume-title":"Diagnostic Imaging in Child Abuse","author":"Marks S C","year":"1998","unstructured":"S C Marks Diagnostic Imaging in Child Abuse, ed P K Kleinman (Mosby, Philadelphia), pp. 2\u20137 (1998)."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(95)80009-F"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10240"},{"key":"e_1_3_3_22_2","first-page":"S39","volume":"154","author":"Kronenberg H M","year":"1997","unstructured":"H M Kronenberg, K Lee, B Lanske, G V Segre J Endocrinol 154,Suppl., S39\u2013S45 (1997).","journal-title":"J Endocrinol"},{"key":"e_1_3_3_23_2","first-page":"283","volume":"53","author":"Kronenberg H M","year":"1998","unstructured":"H M Kronenberg, B Lanske, C S Kovacs, U I Chung, K Lee, G V Segre, E Schipani, H Juppner Recent Prog Horm Res 53, 283\u2013301 (1998).","journal-title":"Recent Prog Horm Res"},{"key":"e_1_3_3_24_2","first-page":"714","volume-title":"The Life of Mammals","author":"Young J Z","year":"1957","unstructured":"J Z Young The Life of Mammals (Oxford Univ. 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