Hyperactive Osteoclasts Cause Osteoporosis In Neurofibromatosis Type 1 Patients

Main Category: Genetics
Also Included In: Bones / Orthopedics
Article Date: 24 Oct 2006 - 22:00 PDT

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Neurofibromatosis type 1 (NF1) is a relatively common genetic disorder (around 1 per 3,000 births) caused by inheriting one mutated copy of the gene NF1. Individuals with NF1 exhibit a range of symptoms, the most severe of which are tumors that grow along certain types of nerves. However, other symptoms, including osteoporosis, are also seen in some individuals.

To understand why individuals expressing only one copy of NF1 (NF1+/-) develop osteoporosis, Wade Clapp and colleagues from Indiana University generated mice expressing only one copy of Nf1 (Nf1+/- mice). Nf1+/- mice were found to have increased numbers of osteoclasts, which are cells that degrade and resorb bone. These osteoclasts were better at surviving, proliferating, and degrading bone than osteoclasts from normal mice. These abnormal characteristics were associated with increased activity of two signaling molecules, p21ras and PI3K. Importantly, in this study, which appears online on October 19 in advance of publication in the November print issue of the Journal of Clinical Investigation, it was shown that osteoclasts from individuals with NF1 have the same characteristics as osteoclasts from Nf1+/- mice. This study not only provides insight into why individuals with NF1 suffer from osteoporosis, but also leads the authors to suggest that targeting PI3K might be a viable therapy for treating all individuals with osteoporosis.

TITLE: Hyperactivity of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions

AUTHOR CONTACT:

D. Wade Clapp
Indiana University School of Medicine, Indianapolis, Indiana, USA.

Feng-Chun Yang
Indiana University School of Medicine, Indianapolis, Indiana, USA.

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JCI table of contents: October 19, 2006

Contact: Karen Honey
Journal of Clinical Investigation

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