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: Diagnosis, Management and Clinical Outcomes
PublisherFuture Medicine Ltd.
Pages15-44
Number of pages30
ISBN (Print)9781634632485, 9781634632294
StatePublished - Oct 1 2014

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

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..