{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:28:15Z","timestamp":1786588095840,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004091","name":"Kumamoto University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004091","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Bone Miner Metab"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Giant cell tumor of bone (GCTB) induces overproduction of bone-resorbing osteoclasts through receptor activator of nuclear factor kappa B ligand (RANKL), leading to bone resorption and destruction. Consequently, denosumab, a neutralizing antibody against RANKL (a cytokine essential for osteoclast induction), is used to treat patients with GCTB. However, the activity of bone formation in GCTB remains poorly understood. Here, we show that GCTB antagonizes bone formation by expressing WNT5B, which inhibits bone formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Co-culture of NCC-GCTB1-C1 (GCTB1s), a human GCTB cell line, with human adipose-derived stem cells (ADSCs) was performed with osteoblast induction medium. To identify the inhibitors of osteoblast differentiation, we reanalyzed the single-cell RNA sequencing data that was previously published. In addition, we performed spatial transcriptome analysis (Visium) against the section of paraffin block of GCTB. The targeted protein was knocked out using CRISPR\/Cas9 and co-culture was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Co-culture of GCTB1s with ADSCs significantly inhibited mineralization of ADSCs. Reanalysis of single-cell RNA sequencing data indicated that GCTB tumors express\n                      <jats:italic>WNT5B,<\/jats:italic>\n                      and we observed that GCTB1s express\n                      <jats:italic>WNT5B<\/jats:italic>\n                      . We then knocked out\n                      <jats:italic>WNT5B<\/jats:italic>\n                      in GCTB1s using CRISPR\/Cas9 and co-cultured them with ADSCs and observed significant rescue of mineralization in ADSCs relative to ADSCs cultured with GCTB1s expressing\n                      <jats:italic>WNT5B<\/jats:italic>\n                      . We also show that ADSC supernatants induce mineralization of GCTB1s.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These studies indicate that GCTB not only induces osteoclasts, but also possesses activity that inhibits bone formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00774-026-01713-3","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T16:19:24Z","timestamp":1774282764000},"page":"455-468","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Giant cell tumor of bone inhibits osteoblastogenesis via WNT5B"],"prefix":"10.1007","volume":"44","author":[{"given":"Masaki","family":"Shimada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Tsuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tateyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Matsunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuka","family":"Homma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasumi","family":"Dainobu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Takata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Takata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntaro","family":"Tanimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junki","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Arima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Karasugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hisanaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Karata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Goshogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Tajiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibiki","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Uehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Yugami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Yonemitsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Tanoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Yamagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"1713_CR1","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/S0046-8177(96)90445-1","volume":"27","author":"VL Fornasier","year":"1996","unstructured":"Fornasier VL, Protzner K, Zhang I, Mason L (1996) The prognostic significance of histomorphometry and immunohistochemistry in giant cell tumors of bone. Hum Pathol 27:754\u2013760","journal-title":"Hum Pathol"},{"key":"1713_CR2","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1309\/BPET-F2PE-P2BD-J3P3","volume":"117","author":"S Roux","year":"2002","unstructured":"Roux S, Amazit L, Meduri G, Guiochon-Mantel A, Milgrom E, Mariette X (2002) RANK (receptor activator of nuclear factor kappa B) and RANK ligand are expressed in giant cell tumors of bone. Am J Clin Pathol 117:210\u2013216","journal-title":"Am J Clin Pathol"},{"key":"1713_CR3","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1053\/S0046-8177(03)00413-1","volume":"34","author":"M W\u00fclling","year":"2003","unstructured":"W\u00fclling M, Delling G, Kaiser E (2003) The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol 34:983\u2013993","journal-title":"Hum Pathol"},{"key":"1713_CR4","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1038\/ng.2814","volume":"45","author":"S Behjati","year":"2013","unstructured":"Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N et al (2013) Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet 45:1479\u20131482","journal-title":"Nat Genet"},{"key":"1713_CR5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ocl.2005.08.005","volume":"37","author":"RE Turcotte","year":"2006","unstructured":"Turcotte RE (2006) Giant cell tumor of bone. Orthop Clin North Am 37:35\u201351","journal-title":"Orthop Clin North Am"},{"key":"1713_CR6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/PAP.0000000000000293","volume":"28","author":"JH Choi","year":"2021","unstructured":"Choi JH, Ro JY (2021) The 2020 WHO classification of tumors of bone: an updated review. Adv Anat Pathol 28:119\u2013138","journal-title":"Adv Anat Pathol"},{"key":"1713_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ctrv.2009.09.002","volume":"36","author":"C Errani","year":"2010","unstructured":"Errani C, Ruggieri P, Asenzio MA, Toscano A, Colangeli S, Rimondi E, Rossi G, Longhi A, Mercuri M (2010) Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev 36:1\u20137","journal-title":"Cancer Treat Rev"},{"key":"1713_CR8","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0002-9440(10)62959-8","volume":"167","author":"T Morgan","year":"2005","unstructured":"Morgan T, Atkins GJ, Trivett MK, Johnson SA, Kansara M, Schlicht SL, Slavin JL, Simmons P, Dickinson I, Powell G, Choong PF, Holloway AJ, Thomas DM (2005) Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. Am J Pathol 167:117\u2013128","journal-title":"Am J Pathol"},{"key":"1713_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-018-1459-6","volume":"16","author":"H Urakawa","year":"2018","unstructured":"Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K et al (2018) Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. World J Surg Oncol 16:160","journal-title":"World J Surg Oncol"},{"key":"1713_CR10","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1196\/annals.1365.035","volume":"1092","author":"DJ Hadjidakis","year":"2006","unstructured":"Hadjidakis DJ, Androulakis II (2006) Bone remodeling. Ann N Y Acad Sci 1092:385\u2013396","journal-title":"Ann N Y Acad Sci"},{"key":"1713_CR11","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/S0092-8674(00)80259-7","volume":"89","author":"F Otto","year":"1997","unstructured":"Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765\u2013771","journal-title":"Cell"},{"key":"1713_CR12","doi-asserted-by":"publisher","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","volume":"95","author":"H Yasuda","year":"1998","unstructured":"Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL. Proc Natl Acad Sci U S A 95:3597\u20133602","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1713_CR13","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1172\/JCI70050","volume":"124","author":"JL Crane","year":"2014","unstructured":"Crane JL, Cao X (2014) Bone marrow mesenchymal stem cells and TGF-\u03b2 signaling in bone remodeling. J Clin Invest 124:466\u2013472","journal-title":"J Clin Invest"},{"key":"1713_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02541-w","volume":"9","author":"M Furuya","year":"2018","unstructured":"Furuya M, Kikuta J, Fujimori S, Seno S, Maeda H et al (2018) Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo. Nat Commun 9:300","journal-title":"Nat Commun"},{"key":"1713_CR15","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1101\/gad.12.9.1260","volume":"12","author":"N Bucay","year":"1998","unstructured":"Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260\u20131268","journal-title":"Genes Dev"},{"key":"1713_CR16","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1242\/jcs.00623","volume":"116","author":"Y Kawano","year":"2003","unstructured":"Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627\u20132634","journal-title":"J Cell Sci"},{"key":"1713_CR17","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s00774-007-0824-2","volume":"26","author":"R Nishimura","year":"2008","unstructured":"Nishimura R, Hata K, Ikeda F, Ichida F, Shimoyama A, Matsubara T, Wada M, Amano K, Yoneda T (2008) Signal transduction and transcriptional regulation during mesenchymal cell differentiation. J Bone Miner Metab 26:203\u2013212","journal-title":"J Bone Miner Metab"},{"key":"1713_CR18","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.devcel.2005.03.016","volume":"8","author":"TF Day","year":"2005","unstructured":"Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt\/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739\u2013750","journal-title":"Dev Cell"},{"key":"1713_CR19","doi-asserted-by":"publisher","first-page":"R167","DOI":"10.1530\/JME-18-0176","volume":"62","author":"G Holdsworth","year":"2019","unstructured":"Holdsworth G, Roberts SJ, Ke HZ (2019) Novel actions of sclerostin on bone. J Mol Endocrinol 62:R167\u2013R185","journal-title":"J Mol Endocrinol"},{"key":"1713_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.115918","volume":"147","author":"S Costa","year":"2021","unstructured":"Costa S, Fairfield H, Farrell M, Murphy CS, Soucy A, Vary C, Holdsworth G, Reagan MR (2021) Sclerostin antibody increases trabecular bone and bone mechanical properties by increasing osteoblast activity damaged by whole-body irradiation in mice. Bone 147:115918","journal-title":"Bone"},{"key":"1713_CR21","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.prp.2009.02.011","volume":"205","author":"S Matsubayashi","year":"2009","unstructured":"Matsubayashi S, Nakashima M, Kumagai K, Egashira M, Naruke Y, Kondo H, Hayashi T, Shindo H (2009) Immunohistochemical analyses of beta-catenin and cyclin D1 expression in giant cell tumor of bone (GCTB): a possible role of Wnt pathway in GCTB tumorigenesis. Pathol Res Pract 205:626\u2013633","journal-title":"Pathol Res Pract"},{"key":"1713_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-17728-5","volume":"12","author":"A Kimura","year":"2022","unstructured":"Kimura A, Toda Y, Matsumoto Y, Yamamoto H, Yahiro K, Shimada E, Kanahori M, Oyama R, Fukushima S, Nakagawa M, Setsu N, Endo M, Fujiwara T, Matsunobu T, Oda Y, Nakashima Y (2022) Nuclear \u03b2-catenin translocation plays a key role in osteoblast differentiation of giant cell tumor of bone. Sci Rep 12:13438","journal-title":"Sci Rep"},{"key":"1713_CR23","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/S0002-9440(10)64942-5","volume":"156","author":"L Huang","year":"2000","unstructured":"Huang L, Xu J, Wood DJ, Zheng MH (2000) Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation. Am J Pathol 156:761\u2013767","journal-title":"Am J Pathol"},{"key":"1713_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06243-6","volume":"23","author":"F Zhao","year":"2025","unstructured":"Zhao F, Chen M, Wu T, Ji M, Li F (2025) Integration of single-cell and bulk RNA sequencing to identify a distinct tumor stem cells and construct a novel prognostic signature for evaluating prognosis and immunotherapy in LUAD. J Transl Med 23:222","journal-title":"J Transl Med"},{"key":"1713_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1477327","volume":"16","author":"H Lin","year":"2024","unstructured":"Lin H, Su L, Mao D, Yang G, Huang Q, Lan Y, Zeng J, Song W, Liang G, Wei Q, Zou D, Li R, Zou C (2024) Identification of altered immune cell types and molecular mechanisms in Alzheimer\u2019s disease progression by single-cell RNA sequencing. Front Aging Neurosci 16:1477327","journal-title":"Front Aging Neurosci"},{"key":"1713_CR26","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.7150\/thno.87201","volume":"14","author":"X Gong","year":"2024","unstructured":"Gong X, Liu Y, Liu H, Cao N, Zeng L, Tian M, Zeng C, Hu Y, Zhang R, Chen Y, Wu G (2024) Re-analysis of single-cell transcriptomics reveals a critical role of macrophage-like smooth muscle cells in advanced atherosclerotic plaque. Theranostics 14:1450\u20131463","journal-title":"Theranostics"},{"key":"1713_CR27","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh9069","volume":"9","author":"H Oyoshi","year":"2023","unstructured":"Oyoshi H, Du J, Sakai SA, Yamashita R, Okumura M et al (2023) Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma. Sci Adv 9:eadh9069","journal-title":"Sci Adv"},{"key":"1713_CR28","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0003-2697(84)90782-6","volume":"138","author":"D Wessel","year":"1984","unstructured":"Wessel D, Fl\u00fcgge UI (1984) A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem 138:141\u2013143","journal-title":"Anal Biochem"},{"key":"1713_CR29","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/jcb.22556","volume":"110","author":"PK Ng","year":"2010","unstructured":"Ng PK, Tsui SK, Lau CP, Wong CH, Wong WH, Huang L, Kumta SM (2010) CCAAT\/enhancer binding protein beta is up-regulated in giant cell tumor of bone and regulates RANKL expression. J Cell Biochem 110:438\u2013446","journal-title":"J Cell Biochem"},{"key":"1713_CR30","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1111\/os.12568","volume":"12","author":"YH Jin","year":"2020","unstructured":"Jin YH, Zhang J, Zhu H, Fan GT, Zhou GX (2020) Functions of exogenous RUNX2 in giant cell tumor of bone in vitro. Orthop Surg 12:668\u2013678","journal-title":"Orthop Surg"},{"key":"1713_CR31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.ajhg.2021.11.018","volume":"109","author":"S Suthon","year":"2022","unstructured":"Suthon S, Lin J, Perkins RS, Crockarell JR Jr., Miranda-Carboni GA, Krum SA (2022) Estrogen receptor alpha and NFATc1 bind to a bone mineral density-associated SNP to repress WNT5B in osteoblasts. Am J Hum Genet 109:97\u2013115","journal-title":"Am J Hum Genet"},{"key":"1713_CR32","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1359\/jbmr.2000.15.4.640","volume":"15","author":"GJ Atkins","year":"2000","unstructured":"Atkins GJ, Haynes DR, Graves SE, Evdokiou A, Hay S, Bouralexis S, Findlay DM (2000) Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res 15:640\u2013649","journal-title":"J Bone Miner Res"},{"key":"1713_CR33","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s00776-005-0946-0","volume":"10","author":"A Murata","year":"2005","unstructured":"Murata A, Fujita T, Kawahara N, Tsuchiya H, Tomita K (2005) Osteoblast lineage properties in giant cell tumors of bone. J Orthop Sci 10:581\u2013588","journal-title":"J Orthop Sci"},{"key":"1713_CR34","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1002\/1097-0142(197005)25:5<1061::AID-CNCR2820250509>3.0.CO;2-E","volume":"25","author":"DC Dahlin","year":"1970","unstructured":"Dahlin DC, Cupps RE, Johnson EW Jr. (1970) Giant-cell tumor: a study of 195 cases. Cancer 25:1061\u20131070","journal-title":"Cancer"},{"key":"1713_CR35","doi-asserted-by":"publisher","first-page":"702","DOI":"10.3109\/10428191003646697","volume":"51","author":"ST Shu","year":"2010","unstructured":"Shu ST, Martin CK, Thudi NK, Dirksen WP, Rosol TJ (2010) Osteolytic bone resorption in adult T-cell leukemia\/lymphoma. Leuk Lymphoma 51:702\u2013714","journal-title":"Leuk Lymphoma"},{"key":"1713_CR36","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1001\/archinte.1988.00380040161023","volume":"148","author":"S Fukumoto","year":"1988","unstructured":"Fukumoto S, Matsumoto T, Ikeda K, Yamashita T, Watanabe T, Yamaguchi K, Kiyokawa T, Takatsuki K, Shibuya N, Ogata E (1988) Clinical evaluation of calcium metabolism in adult T-cell leukemia\/lymphoma. Arch Intern Med 148:921\u2013925","journal-title":"Arch Intern Med"},{"key":"1713_CR37","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1182\/blood.V99.2.634","volume":"99","author":"K Nosaka","year":"2002","unstructured":"Nosaka K, Miyamoto T, Sakai T, Mitsuya H, Suda T, Matsuoka M (2002) Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappaB ligand on adult T-cell leukemia cells. Blood 99:634\u2013640","journal-title":"Blood"},{"key":"1713_CR38","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s00223-012-9599-0","volume":"91","author":"SH Ralston","year":"2012","unstructured":"Ralston SH, Layfield R (2012) Pathogenesis of Paget disease of bone. Calcif Tissue Int 91:97\u2013113","journal-title":"Calcif Tissue Int"},{"key":"1713_CR39","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.beem.2018.05.005","volume":"32","author":"NM Appelman-Dijkstra","year":"2018","unstructured":"Appelman-Dijkstra NM, Papapoulos SE (2018) Paget\u2019s disease of bone. Best Pract Res Clin Endocrinol Metab 32:657\u2013668","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"1713_CR40","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1172\/JCI115305","volume":"88","author":"R Bataille","year":"1991","unstructured":"Bataille R, Chappard D, Marcelli C, Dessauw P, Baldet P, Sany J, Alexandre C (1991) Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma. J Clin Invest 88:62\u201366","journal-title":"J Clin Invest"},{"key":"1713_CR41","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1056\/NEJMoa030847","volume":"349","author":"E Tian","year":"2003","unstructured":"Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr. (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483\u20132494","journal-title":"N Engl J Med"},{"key":"1713_CR42","doi-asserted-by":"publisher","first-page":"5124","DOI":"10.1073\/pnas.0911929107","volume":"107","author":"S Vallet","year":"2010","unstructured":"Vallet S, Mukherjee S, Vaghela N, Hideshima T, Fulciniti M et al (2010) Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci U S A 107:5124\u20135129","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1713_CR43","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","volume":"149","author":"H Clevers","year":"2012","unstructured":"Clevers H, Nusse R (2012) Wnt\/\u03b2-catenin signaling and disease. Cell 149:1192\u20131205","journal-title":"Cell"},{"key":"1713_CR44","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1007\/s13577-021-00639-4","volume":"35","author":"T Ono","year":"2022","unstructured":"Ono T, Noguchi R, Yoshimatsu Y, Tsuchiya R, Sin Y, Nakagawa R, Hirabayashi K, Ozawa I, Kikuta K, Kondo T (2022) Establishment and characterization of the NCC-GCTB4-C1 cell line: a novel patient-derived cell line from giant cell tumor of bone. Hum Cell 35:392\u2013399","journal-title":"Hum Cell"},{"key":"1713_CR45","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1359\/jbmr.060819","volume":"21","author":"H Aslan","year":"2006","unstructured":"Aslan H, Ravid-Amir O, Clancy BM, Rezvankhah S, Pittman D, Pelled G, Turgeman G, Zilberman Y, Gazit Z, Hoffmann A, Gross G, Domany E, Gazit D (2006) Advanced molecular profiling in vivo detects novel function of dickkopf-3 in the regulation of bone formation. J Bone Miner Res 21:1935\u20131945","journal-title":"J Bone Miner Res"},{"key":"1713_CR46","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.biopha.2017.06.061","volume":"93","author":"Q Xiao","year":"2017","unstructured":"Xiao Q, Chen Z, Jin X, Mao R, Chen Z (2017) The many postures of noncanonical Wnt signaling in development and diseases. Biomed Pharmacother 93:359\u2013369","journal-title":"Biomed Pharmacother"},{"key":"1713_CR47","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/nm.2653","volume":"18","author":"K Maeda","year":"2012","unstructured":"Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, Kikuchi Y, Takada I, Kato S, Kani S, Nishita M, Marumo K, Martin TJ, Minami Y, Takahashi N (2012) Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nat Med 18:405\u2013412","journal-title":"Nat Med"},{"key":"1713_CR48","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1242\/dev.126.6.1211","volume":"126","author":"TP Yamaguchi","year":"1999","unstructured":"Yamaguchi TP, Bradley A, McMahon AP, Jones S (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126:1211\u20131223","journal-title":"Development"},{"key":"1713_CR49","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.bbrc.2011.11.089","volume":"417","author":"F Santiago","year":"2012","unstructured":"Santiago F, Oguma J, Brown AM, Laurence J (2012) Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir. Biochem Biophys Res Commun 417:223\u2013230","journal-title":"Biochem Biophys Res Commun"},{"key":"1713_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/srep04493","volume":"4","author":"M Okamoto","year":"2014","unstructured":"Okamoto M, Udagawa N, Uehara S, Maeda K, Yamashita T, Nakamichi Y, Kato H, Saito N, Minami Y, Takahashi N, Kobayashi Y (2014) Noncanonical Wnt5a enhances Wnt\/\u03b2-catenin signaling during osteoblastogenesis. Sci Rep 4:4493","journal-title":"Sci Rep"}],"container-title":["Journal of Bone and Mineral Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-026-01713-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00774-026-01713-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-026-01713-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:01:32Z","timestamp":1786586492000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00774-026-01713-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["1713"],"URL":"https:\/\/doi.org\/10.1007\/s00774-026-01713-3","relation":{},"ISSN":["0914-8779","1435-5604"],"issn-type":[{"value":"0914-8779","type":"print"},{"value":"1435-5604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"1 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors have no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}