Activin A is an essential cofactor for osteoclast induction.
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.
Fuller
K
K
Department of Histopathology, St. George's Hospital Medical School, London, SW17 ORE, United Kingdom. k.fuller@sghms.ac.uk
Bayley
K E
KE
Chambers
T J
TJ
D030301:Activin Receptors, Type II; D028341:Activins; D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007265:Inhibins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017978:Receptors, Growth Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D028341:Activins; D007265:Inhibins; D016173:Macrophage Colony-Stimulating Factor; D030301:Activin Receptors, Type II