Skeletal Complications in Neurofibromatosis Type 1: the Role of Neurofibromin Haploinsufficiency in Defective Skeletal Remodeling and Bone Healing in NF1

Abstract

A large proportion of patients with Neurofibromatosis Type 1 display skeletal abnormalities including scoliosis and pseudoarthrosis, which are compounded by osteoporosis and poor bone healing. Corrective orthopaedic intervention often fails, necessitating multiple revision surgeries followed by prolonged recovery periods. The cell types and pathway by which neurofibromin haploinsufficiency (Nf1 +/-) leads to dysregulation of bone remodeling and healing are unknown. The aim of this study is to identify the cell types expressing Nf1 in normal bone cell physiology and fracture healing and to test the Nf1 requirement in vitro. We have employed in vitro and in vivo models to test the effects of neurofibromin deficiency in bone-forming osteoblasts and in bone-resorbing osteoblast cells. In addition, we have established a collection of bone tissue samples from NF1 patients to characterize the bone, tissue, and cells of NF1 bone.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2009
Accession Number
ADA506315

Entities

People

  • Kevin P. Mchugh

Organizations

  • Beth Israel Deaconess Medical Center

Tags

DTIC Thesaurus Topics

  • Bone And Bones
  • Bone Diseases
  • Bone Fractures
  • Cell Physiology
  • Cells
  • Connective Tissue Cells
  • Diseases And Disorders
  • Health Services
  • Intervention
  • Macrophages
  • Medical Personnel
  • Orthopedics
  • Osteoblasts
  • Osteogenesis
  • Physiology
  • Research Facilities

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Molecular and Cellular Biology
  • Trauma Surgery or Emergency Medicine.