Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts

Sci Rep. 2017 Jul 17;7(1):5526. doi: 10.1038/s41598-017-05835-7.


Tissue microenvironments formed by extracellular matrix networks play an important role in regulating tissue structure and function. Extracellular microfibrillar networks composed of fibrillins and their associated ligands such as LTBPs, fibulins, and EMILINs are of particular interest in this regard since they provide a specialized cellular microenvironment guiding proper morphology and functional behavior of specialized cell types. To understand how cellular microenvironments composed of intricate microfibrillar networks influence cell fate decisions in a contextual manner, more information about the spatiotemporal localization, deposition, and function of their components is required. By employing confocal immunofluorescence and electron microscopy we investigated the localization and extracellular matrix deposition of EMILIN-1 and -2 in tissues of the skeletal system such as cartilage and bone as well as in in vitro cultures of osteoblasts. We found that upon RNAi mediated depletion of EMILIN-1 in primary calvarial osteoblasts and MC3T3-E1 cells only fibulin-4 matrix deposition was lost while other fibulin family members or LTBPs remained unaffected. Immunoprecipitation and ELISA-style binding assays confirmed a direct interaction between EMILIN-1 and fibulin-4. Our data suggest a new function for EMILIN-1 which implies the guidance of linear fibulin-4 matrix deposition and thereby fibulin-4 fiber formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / metabolism
  • Calcium-Binding Proteins / antagonists & inhibitors
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cartilage / metabolism
  • Cell Line
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • Latent TGF-beta Binding Proteins / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism


  • Calcium-Binding Proteins
  • EFEMP2 protein, human
  • Extracellular Matrix Proteins
  • Latent TGF-beta Binding Proteins
  • Membrane Glycoproteins
  • RNA, Small Interfering
  • elastin microfibril interface located protein
  • fibulin 2