Exogenous noggin binds the BMP-2 receptor and induces alkaline phosphatase activity in osteoblasts

J Cell Biochem. 2019 Aug;120(8):13237-13242. doi: 10.1002/jcb.28597. Epub 2019 Mar 19.

Abstract

Osteogenesis is an important process in bone remodeling and is under strict cellular signaling governed by growth factors and antagonists. Bone morphogenetic protein 2 (BMP-2) is an important osteogenic factor involved in the transcription of key osteogenic genes such as alkaline phosphatase (ALP). While, antagonists such as noggin effectively restrict osteoblast differentiation through binding to BMP-2. In this study, we sought to understand the effect of exogenous noggin in osteoblasts and its role in BMP-2 activation of osteogenesis. Enzymatic activity of ALP was monitored to ascertain the effect of the noggin. Fluorescently labelled noggin was used to determine the binding of noggin to the BMP-2 receptor. The results demonstrated that noggin significantly increases the activity of ALP at concentrations of 50 to 400 ng/mL. While, it inhibited the activity of exogenous BMP-2. Furthermore, fluorescently labelled noggin showed strong binding to osteoblasts which were perturbed when cells were preincubated with BMP-2 suggesting that noggin shares a common receptor with BMP-2. These results suggest that exogenous noggin facilitates osteogenic differentiation and provide a novel mechanism for its interplay with BMP-2.

Keywords: bone morphogenetic protein; cell differentiation; noggin; osteoblasts; osteogenesis.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism*
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Humans
  • Microscopy, Fluorescence
  • Osteoblasts / metabolism*
  • Protein Binding

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Carrier Proteins
  • noggin protein
  • Alkaline Phosphatase