Marco Eijken

The activin A-follistatin system: potent regulator of human extracellular matrix mineralization

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review


  • Marco Eijken
  • Sigrid Swagemakers
  • ,
  • Marijke Koedam
  • ,
  • Cobie Steenbergen
  • ,
  • Pieter Derkx
  • ,
  • André G Uitterlinden
  • ,
  • Peter J van der Spek
  • ,
  • Jenny A Visser
  • ,
  • Frank H de Jong
  • ,
  • Huibert A P Pols
  • ,
  • Johannes P T M van Leeuwen

Bone quality is an important determinant of osteoporosis, and proper osteoblast differentiation plays an important role in the control and maintenance of bone quality. We investigated the impact of activin signaling on human osteoblast differentiation, extracellular matrix formation, and mineralization. Activins belong to the transforming growth factor-beta superfamily and activin A treatment strongly inhibited mineralization in osteoblast cultures, whereas the activin antagonist follistatin increased mineralization. Osteoblasts produced activin A and follistatin in a differentiation-dependent manner, leading to autocrine regulation of extracellular matrix formation and mineralization. In addition, mineralization in a vascular smooth muscle cell-based model for pathological calcification was inhibited. Comparative activin A and follistatin gene expression profiling showed that activin signaling changes the expression of a specific range of extracellular matrix proteins prior to the onset of mineralization, leading to a matrix composition with reduced or no mineralizing capacity. These findings demonstrate the regulation of osteoblast differentiation and matrix mineralization by the activin A-follistatin system, providing the possibility to control bone quality as well as pathological calcifications such as atherosclerosis by using activin A, follistatin, or analogs thereof.

TidsskriftFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Sider (fra-til)2949-60
Antal sider12
StatusUdgivet - sep. 2007
Eksternt udgivetJa

Se relationer på Aarhus Universitet Citationsformater

ID: 172631312