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Aberrant Myeloid Differentiation Contributes to the Development of Osteoporosis in Neurofibromatosis Type 1

  • Epidemiology and Pathophysiology (J Cauley and B Dawson-Hughes, Section Editors)
  • Published:
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Abstract

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a common autosomal dominant genetic disorder affecting approximately 1 in 3000 individuals worldwide. NF1 results from heritable or spontaneous mutations of the NF1 tumor suppressor gene. NF1 encodes the protein neurofibromin, which functions to negatively regulate Ras-activity. Approximately 50 % of NF1 patients develop osteopenia or osteoporosis, resulting in significantly increased rates of long-bone fracture and morbidity. While defective osteoblast bone anabolism has been implicated as a central factor in the pathogenesis of NF1 associated skeletal deficits, recent data suggest that NF1 (Nf1) haploinsufficiency within the hematopoietic compartment, particularly in osteoclasts and myeloid progenitors, plays a pivotal role in engendering NF1 osseous manifestations. In this chapter, we review the latest data from clinical studies and murine models delineating a critical role for hematopoietic compartment, myeloid progenitors of NF1 (Nf1) haploinsufficient and their progeny-osteoclasts, in the pathogenesis of NF1 associated osteopenia/osteoporosis and discuss putative targets for future therapeutics.

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Authors and Affiliations

  1. Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    Steven D. Rhodes

  2. Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, R. Bunn Gautier Building, 417 1011 NW 15th street, Locator R-629, Miami, FL, 33136, USA

    Feng-Chun Yang

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  2. Feng-Chun Yang
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Correspondence to Feng-Chun Yang.

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Steven D. Rhodes and Feng-Chun Yang declare that they have no conflict of interest.

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This article is part of the Topical Collection on Epidemiology and Pathophysiology

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Rhodes, S.D., Yang, FC. Aberrant Myeloid Differentiation Contributes to the Development of Osteoporosis in Neurofibromatosis Type 1. Curr Osteoporos Rep 14, 10–15 (2016). https://doi.org/10.1007/s11914-016-0298-z

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