Publication Date:
2004-11-16
Description:
Patients with neurofibromatosis type 1 (NF1) have mutations in the NF1 tumor-suppressor gene that functions as a GTPase activating protein (GAP) for p21ras. Individuals with NF1 display a variety of skeletal defects including lytic bone lesions. However, the effect of loss of NF1 on osteoclasts or osteoblasts, the two principal cells involved in bone remodeling, is not understood. Osteoclasts are specialized myeloid cells that adhere to bone matrix, and secrete lytic enzymes that degrade bone. Given that we have previously identified haploinsufficient phenotypes in Nf1 +/− mast cells, we defined the role of neurofibromin in regulating various osteoclast functions in vitro and in vivo in Nf1 +/− mice. Strikingly, histologic sections from femurs of Nf1 +/− mice, revealed large numbers of multinucleated osteoclasts. This phenotype is reminiscent of the osteoclasts in patients with Paget’s disease and of osteoclasts isolated from SHIP deficient mice, which have elevated levels of PI-3K activity. Additionally, osteoclast progenitors from Nf1 +/− mice were hyperresponsive to limiting concentrations of M-CSF and RANKL and formed higher numbers of OCL progenitors compared to +/+ controls (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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