{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:04:43Z","timestamp":1784642683969,"version":"3.55.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T00:00:00Z","timestamp":1430092800000},"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":[[2015,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Although nullizygous loss of NF1 leads to myeloid malignancies, haploinsufficient loss of NF1 (Nf1) has been shown to contribute to osteopenia and osteoporosis which occurs in approximately 50% of neurofibromatosis type 1 (NF1) patients. Bone marrow mononuclear cells of haploinsufficient NF1 patients and Nf1+\/\u2013 mice exhibit increased osteoclastogenesis and accelerated bone turnover; however, the culprit hematopoietic lineages responsible for perpetuating these osteolytic manifestations have yet to be elucidated. Here we demonstrate that conditional inactivation of a single Nf1 allele within the myeloid progenitor cell population (Nf1-LysM) is necessary and sufficient to promote multiple osteoclast gains-in-function, resulting in enhanced osteoclastogenesis and accelerated osteoclast bone lytic activity in response to proresorptive challenge in vivo. Surprisingly, mice conditionally Nf1 heterozygous in mature, terminally differentiated osteoclasts (Nf1-Ctsk) do not exhibit any of these skeletal phenotypes, indicating a critical requirement for Nf1 haploinsufficiency at a more primitive\/progenitor stage of myeloid development in perpetuating osteolytic activity. We further identified p21Ras-dependent hyperphosphorylation of Pu.1 within the nucleus of Nf1 haploinsufficient myelomonocytic osteoclast precursors, providing a novel therapeutic target for the potential treatment of NF1 associated osteolytic manifestations. \u00a9 2015 American Society for Bone and Mineral Research<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2538","type":"journal-article","created":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T12:03:34Z","timestamp":1430136214000},"page":"1840-1851","source":"Crossref","is-referenced-by-count":5,"title":["<i>Nf1<\/i> Haploinsufficiency Alters Myeloid Lineage Commitment and Function, Leading to Deranged Skeletal Homeostasis"],"prefix":"10.1093","volume":"30","author":[{"given":"Steven D","family":"Rhodes","sequence":"first","affiliation":[{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"},{"name":"Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshav","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaomin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl W","family":"Staser","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Peng","sequence":"additional","affiliation":[{"name":"Endocrinology and MetabolismDepartment of Internal MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid S","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Endocrinology and MetabolismDepartment of Internal MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A","family":"Guise","sequence":"additional","affiliation":[{"name":"Endocrinology and MetabolismDepartment of Internal MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Department of PediatricsIndiana University School of MedicineIndianapolisINUSA"},{"name":"Herman B. 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