{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:00:29Z","timestamp":1768870829220,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2010,8,20]],"date-time":"2010-08-20T00:00:00Z","timestamp":1282262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Infantile malignant osteopetrosis (IMO) is caused by lack of functional osteoclasts leading to skeletal abnormalities, blindness owing to compression of the optic nerves, bone marrow (BM) failure, and early death. In most patients, TCIRG1, a proton pump subunit essential for bone resorption, is mutated. oc\/oc mice represent a model for IMO owing to a deletion in Tcirg1 and die around 4 weeks of age. To determine if hematopoietic stem cell transplantation without prior conditioning can reverse osteopetrosis, neonatal mice were transplanted intravenously with lineage-depleted BM cells. More than 85% of oc\/oc mice transplanted with 5\u2009\u00d7\u2009106 cells survived long term with an engraftment of 3% to 5% in peripheral blood (PB). At 3 weeks, engraftment in the BM was 1% to 2%, but the cellularity had increased 60-fold compared with untreated oc\/oc mice, and RANKL and macrophage colony-stimulating factor (M-CSF) expression in the BM was normalized. Histopathology and micro\u2013computed tomography revealed almost complete reversal of osteopetrosis after 4 weeks. In vitro studies showed that bone resorption by osteoclasts from transplanted oc\/oc mice was 14% of transplanted controls, and immunofluorescence microscopy revealed that resorption was mainly associated with osteoclasts of donor origin. Lineage analysis of BM, PB, and spleen did not provide any evidence for selective recruitment of cells to the osteoclastic lineage. The vision also was preserved in transplanted oc\/oc mice, as determined by a visual tracking drum test. In summary, nonablative neonatal transplantation leading to engraftment of only a small fraction of normal cells rapidly reverses severe osteopetrosis in the oc\/oc mouse model. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.90","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T18:33:40Z","timestamp":1277145220000},"page":"2069-2077","source":"Crossref","is-referenced-by-count":11,"title":["Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low-level engraftment and lack of selective expansion of the osteoclastic lineage"],"prefix":"10.1093","volume":"25","author":[{"given":"Carmen","family":"Flores","sequence":"first","affiliation":[{"name":"Molecular Medicine and Gene Therapy, Lund Stem Cell Center, University of Lund, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teun J","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilana","family":"Moscatelli","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Gene Therapy, Lund Stem Cell Center, University of Lund, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Askmyr","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Gene Therapy, Lund Stem Cell Center, University of Lund, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ton","family":"Schoenmaker","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geerling EJ","family":"Langenbach","sequence":"additional","affiliation":[{"name":"Department of Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats","family":"Ehinger","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital of Lund, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Everts","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Amsterdam, The 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