Multiple increased osteoclast functions in individuals with neurofibromatosis type 1

David A. Stevenson, Jincheng Yan, Yongzheng He, Huijie Li, Yaling Liu, Qi Zhang, Yongmin Jing, Zhiping Guo, Wei Zhang, Dalong Yang, Xiaohua Wu, Heather Hanson, Xiaohong Li, Karl Staser, David H. Viskochil, John C. Carey, Shi Chen, Lucy Miller, Kent Roberson, Laurie Moyer-MileurMenggang Yu, Elisabeth L. Schwarz, Marzia Pasquali, Feng Chun Yang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Skeletal abnormalities including scoliosis, tibial dysplasia, sphenoid wing dysplasia, and decreased bone mineral density (BMD) are associated with neurofibromatosis type 1 (NF1). We report the cellular phenotype of NF1 human-derived osteoclasts and compare the in vitro findings with the clinical phenotype. Functional characteristics (e.g., osteoclast formation, migration, adhesion, resorptive capacity) and cellular mechanistic alterations (e.g., F-actin polymerization, MAPK phosphorylation, RhoGTPase activity) from osteoclasts cultured from peripheral blood of individuals with NF1 (N=75) were assessed. Osteoclast formation was compared to phenotypic, radiologic, and biochemical data. NF1 osteoprogenitor cells demonstrated increased osteoclast forming capacity. Human NF1-derived osteoclasts demonstrated increased migration, adhesion, and in vitro bone resorption. These activities coincided with increased actin belt formation and hyperactivity in MAPK and RhoGTPase pathways. Although osteoclast formation was increased, no direct correlation of osteoclast formation with BMD, markers of bone resorption, or the clinical skeletal phenotype was observed suggesting that osteoclast formation in vitro cannot directly predict NF1 skeletal phenotypes. While NF1 haploinsufficiency produces a generalized osteoclast gain-in-function and may contribute to increased bone resorption, reduced BMD, and focal skeletal defects associated with NF1, additional and perhaps local modifiers are likely required for the development of skeletal abnormalities in NF1.

Original languageEnglish (US)
Pages (from-to)1050-1059
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Issue number5
StatePublished - May 2011
Externally publishedYes


  • Bone mineral density
  • Bone resorption
  • Neurofibromatosis type 1
  • Osteoporosis
  • Ras

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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