Inhibitory effects of activin-A on osteoblast differentiation during cultures of fetal rat calvarial cells

J Cell Biochem. 1999 Nov 1;75(2):206-14. doi: 10.1002/(sici)1097-4644(19991101)75:2<206::aid-jcb3>;2-k.


Activin-A is a member of the transforming growth factor-beta (TGF-beta) superfamily and is expressed by osteoblasts. However, the role of activin-A on osteoblasts is not clearly understood. We examined the effects of activin-A on osteoblast proliferation or differentiation, and mineralization by the osteoblasts in the first subcultures of fetal rat osteoblasts obtained from calvarial bones. Exogenous activin-A led to impaired formation of bone nodules in a dose-dependent manner, although it did not influence cell proliferation using an MTT assay. This inhibitory effect depended upon the time at which activin-A was added to the culture media, and the effect was most significant when addition took place at the early phase of the culture. In addition, exogenous activin-A inhibited gene expression of type I procollagen, alkaline phosphatase, osteonectin, and osteopontin in the cultured cells using Northern blot analysis. The peak of osteocalcin mRNA was delayed. Gene expression for TGF-beta was not influenced by exogenous activin-A. The betaA subunit (activin-A) mRNA was detected during the early phase of this culture. These results indicate that activin-A inhibited early differentiation of the fetal rat calvarial cells, or osteoblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins
  • Alkaline Phosphatase / pharmacology
  • Animals
  • Bone and Bones / drug effects
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Inhibins / pharmacology*
  • Osteoblasts / drug effects*
  • Osteocalcin / pharmacology
  • Osteonectin / pharmacology
  • Osteopontin
  • Procollagen / pharmacology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Sialoglycoproteins / pharmacology
  • Skull / drug effects*
  • Skull / embryology
  • Time Factors


  • Osteonectin
  • Procollagen
  • RNA, Messenger
  • Sialoglycoproteins
  • Spp1 protein, rat
  • Activins
  • Osteocalcin
  • Osteopontin
  • Inhibins
  • Alkaline Phosphatase