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

摘要

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.