Bone development in neurofibromatosis 1.

Bony abnormalities are common findings in cases of neurofibromatosis 1. We might hypothesize that neurofibromin, the protein encoded by the neurofibromatosis 1 gene, plays important roles in bone development. Loss of function of oligodendrocyte-myelin glycoprotein gene and increased activity of ras p21 might increase the level of c-fos proto-oncogene in bones with formation of fibrous dysplasia-like tissue. Also, increased ras p21 might disturb collagen I synthesis by osteoblasts. Moreover, increased ras activity might increase the mitogenic signals to the nucleus through mitogen-activated protein kinase (MAPK) and disturb the level of the transcription factor core-binding factor alpha(1) (Cbfa1). Abnormal fibrous tissue and neurofibromas formed at the site of pseudarthrosis might represent abnormal response of periosteal fibroblasts for injury, an effect simulating the response of skin fibroblasts in neurofibromatosis 1 to injury. Copyright 2003 Published by Elsevier Science Ltd.