Ras dependent paracrine secretion of osteopontin by nf1 +/- osteoblasts promote osteodast activation in a neurofibromatosis type i murine model

Huijie Li, Yaling Liu, Qi Zhang, Yongmin Jing, Shi Chen, Zhaohui Song, Jincheng Yan, Yan Li, Xiaohua Wu, Xianghong Zhang, Yingze Zhang, Jamie Case, Menggang Yu, David A. Ingram, Feng Chun Yang

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Neurofibromatosis type 1 (NF1) is a pandemic genetic disorder characterized by malignant and nonmalignant manifestations, including skeletal abnormalities, such as osteoporosis, scolio-sis, short stature, and pseudarthrosis. Recent studies in genetically inbred mice and from human patients with NF1 have identified multiple-gains in osteoclast (OCL) functions both in vitro and in vivo. Given that osteoblasts secrete cytokines that promote OCL maturation/activation, we sought to identify whether haploinsufficiency of Nf1 (Nf1+/-) osteoblasts and their precursors secrete cytokines that have a central role in this process. Osteoblast conditioned media (OBCM) from Nf1+/- osteoblasts promoted OCL migration and bone resorption compared with WT OBCM. Osteopontin (OPN), a matrix protein found in mineralized tissues and pivotal in modulating OCL functions, was present in increased concentrations in Nf1 +/- osteoblasts. Addition of OPN neutralizing antibody to Nf1+/- OBCM diminished the gain in bioactivity on OCL functions, including OCL migration and bone resorption. Our study identifies an important paracrine loop whereby elevated secretion of OPN by osteoblasts activate Nf1+/- OCLs that already have an intrinsic propensity for bone resorption leading to osteopenia and osteoporosis. {Pediatr Res 65: 613-618, 2009)

Original languageEnglish (US)
Pages (from-to)613-618
Number of pages6
JournalPediatric Research
Volume65
Issue number6
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Li, H., Liu, Y., Zhang, Q., Jing, Y., Chen, S., Song, Z., Yan, J., Li, Y., Wu, X., Zhang, X., Zhang, Y., Case, J., Yu, M., Ingram, D. A., & Yang, F. C. (2009). Ras dependent paracrine secretion of osteopontin by nf1 +/- osteoblasts promote osteodast activation in a neurofibromatosis type i murine model. Pediatric Research, 65(6), 613-618. https://doi.org/10.1203/PDR.0b013e3181a1c607