Activin A is an essential cofactor for osteoclast induction

Biochem Biophys Res Commun. 2000 Feb 5;268(1):2-7. doi: 10.1006/bbrc.2000.2075.


Recently, receptor activator of NF-kappaB ligand (RANKL) was shown to be necessary for osteoclast formation. We now report that activin A, a cytokine enriched in bone matrix and secreted by osteoblasts and osteoclasts, powerfully synergized with RANKL for induction of osteoclast-like cells (OCL) from bone marrow precursors depleted of stromal cells. Moreover, OCL formation in RANKL was virtually abolished by soluble type II A activin receptors (ActR-II(A)), suggesting that activin A is essential for OCL formation. Activin A was most effective when precursors were exposed to RANKL and activin A simultaneously: resistance to OCL-induction that occurs when precursors are pre-incubated in M-CSF was reduced. Incubation on bone matrix also enhanced the sensitivity of precursors to OCL-induction by RANKL; and this was prevented by soluble ActR-II(A). Thus, activin A in bone matrix, or released from osteoblastic or other cells, enhances the osteoclast-forming potential of precursors and synergizes with RANKL in inducing osteoclastic differentiation.

MeSH terms

  • Activin Receptors, Type II
  • Activins
  • Animals
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Drug Synergism
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology
  • Inhibins / administration & dosage
  • Inhibins / pharmacology
  • Inhibins / physiology*
  • Macrophage Colony-Stimulating Factor / administration & dosage
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Membrane Glycoproteins / administration & dosage
  • Membrane Glycoproteins / pharmacology
  • Membrane Glycoproteins / physiology
  • Mice
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects
  • Osteoclasts / physiology
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Growth Factor / physiology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology


  • Carrier Proteins
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Growth Factor
  • Recombinant Proteins
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Activins
  • Inhibins
  • Macrophage Colony-Stimulating Factor
  • Activin Receptors, Type II