FLT3 ligand can substitute for macrophage colony-stimulating factor in support of osteoclast differentiation and function
- 1 November 2001
- journal article
- Published by American Society of Hematology in Blood
- Vol. 98 (9), 2707-2713
- https://doi.org/10.1182/blood.v98.9.2707
Abstract
Although bone resorption and osteoclast numbers are reduced in osteopetrotic (op/op) mice, osteoclasts are nevertheless present and functional, despite the absence of macrophage colony-stimulating factor (M-CSF). This suggests that alternative factors can partly compensate for the crucial actions of M-CSF in osteoclast induction. It was found that when nonadherent bone marrow cells were incubated in RANKL with Flt3 ligand (FL) without exogenous M-CSF, tartrate-resistance acid phosphatase (TRAP)–positive cells were formed, and bone resorption occurred. Without FL, only macrophagelike TRAP-negative cells were present. Granulocyte-macrophage CSF, stem cell factor, interleukin-3, and vascular endothelial growth factor could not similarly replace the need for M-CSF. TRAP-positive cell induction in FL was not due to synergy with M-CSF produced by the bone marrow cells themselves because FL also enabled their formation from the hemopoietic cells of op/op mice, which lack any M-CSF. FL appeared to substitute for M-CSF by supporting the differentiation of adherent cells that express mRNA for RANK and responsiveness to RANKL. To determine whether FL can account for the compensation for M-CSF deficiency that occurs in vivo, FL signaling was blockaded in op/op mice by the injection of soluble recombinant Flt3. It was found that the soluble receptor induced a substantial decrease in osteoclast number, strongly suggesting that FL is responsible for the partial compensation for M-CSF deficiency that occurs in these mice.This publication has 52 references indexed in Scilit:
- The Regulation of Osteoclastic Development and FunctionCiba Foundation symposium, 2007
- CFU-GM-Derived Cells Form Osteoclasts at a Very High EfficiencyBiochemical and Biophysical Research Communications, 2000
- Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone ResorptionThe Journal of Experimental Medicine, 1999
- Granulocyte-macrophage colony-stimulating factor corrects macrophage deficiencies, but not osteopetrosis, in the colony-stimulating factor-1- deficient op/op mouseEndocrinology, 1994
- Dexamethasone stimulates osteoclast-like cell formation by inhibiting granulocyte-macrophage colony-stimulating factor production in mouse bone marrow culturesEndocrinology, 1994
- Identification of a functional mononuclear precursor of the osteoclast in chicken medullary bone marrow culturesJournal of Bone and Mineral Research, 1992
- Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation.JCI Insight, 1992
- Macrophage colony stimulating factor (M-CSF) is essential for osteoclast formation in vitroBiochemical and Biophysical Research Communications, 1991
- Effect of arachidonic acid metabolites on bone resorption by isolated rat osteoclastsJournal of Bone and Mineral Research, 1989
- Bone matrix stimulates osteoclastic differentiation in cultures of rabbit bone marrow cellsJournal of Bone and Mineral Research, 1989