Hematopoietic lineages cooperate with osteoblasts in the initiation and progression of neurofibromatosis type 1 associated skeletal deficits

Steven David Rhodes, Feng Chun Yang

Research output: Chapter in Book/Report/Conference proceedingChapter

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, encoding the protein neurofibromin, which functions to negatively regulate Ras-activity. Although neurofibromas are considered the hallmark feature of NF1, up to 70 percent of NF1 patients develop both generalized and focal osseous defects including short stature, kyphoscoliosis, osteopenia/osteoporosis, fractures, and pseudarthrosis (fracture non-union). While defective osteoblast bone anabolism has been implicated as a central factor in the pathogenesis of NF1 associated skeletal deficits, recent data suggests 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 demonstrating a requirement for hematopoietic derived NF1 (Nf1) haploinsufficient osteoclasts and their progenitors in the pathogenesis of multiple NF1 skeletal deficits.

Original languageEnglish (US)
Title of host publicationNeurofibromatosis
Subtitle of host publicationDiagnosis, Management and Clinical Outcomes
PublisherFuture Medicine Ltd.
Pages15-44
Number of pages30
ISBN (Electronic)9781634632485
ISBN (Print)9781634632294
StatePublished - Oct 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Rhodes, S. D., & Yang, F. C. (2014). Hematopoietic lineages cooperate with osteoblasts in the initiation and progression of neurofibromatosis type 1 associated skeletal deficits. In Neurofibromatosis: Diagnosis, Management and Clinical Outcomes (pp. 15-44). Future Medicine Ltd..