TY - JOUR
T1 - Macrophage lineage phenotypes and osteoclastogenesis-Complexity in the control by GM-CSF and TGF-beta
AU - Lari, Roya
AU - Fleetwood, Andrew J
AU - Kitchener, Peter D
AU - Cook, Andrew D
AU - Pavasovic, Durda
AU - Hertzog, Paul John
AU - Hamilton, J
PY - 2007
Y1 - 2007
N2 - Bone-resorbing osteoclasts (OCs) derive from macrophage lineage precursors under the potential control of many factors. Addition of macrophage-colony stimulating factor (M-CSF or CSF-1) to murine bone marrow cells gives rise to so-called bone marrow-derived macrophages (BMM); this adherent population can then be quantitatively converted into OC lineage cells when receptor activator of NF kappa B ligand (RANKL) is included. The effect of another CSF, granulocyte macrophage-CSF (GM-CSF), on OC differentiation in vitro is quite complex with both enhancing and suppressive actions being described. We report here that GM-CSF can generate a population of adherent macrophage lineage cells from murine bone marrow precursors (GM-BMM) which is also capable of giving rise to OC lineage cells in the presence of M-CSF and RANKL as effectively as BMM. The degree of this differentiation was surprising considering that GM-BMM are often referred to as immature dendritic cells and that, for both BMM and the GM-BMM, GM-CSF suppressed subsequent OC differentiation governed by M-CSF and RANKL. Unlike for BMM. this GM-CSF-mediated suppression for GM-BMM appeared to be independent of c-fibs expression. The effects on bone of another cytokine, transforming growth factor-beta (TGF-beta), are also quite complex although usually found to be stimulatory for OC differentiation. Unexpectedly, we observed that TGF-beta 1 also potently suppressed M-CSF+RANKL-driven OC differentiation from both BMM and GM-BMM. Using cells from gene-deficient mice, this inhibition of OC differentiation by both GM-CSF and TGF-beta 1 appeared to be independent of endogenous interferon alpha/beta production. It appears therefore that the influence of GM-CSF and TGF-beta on osteoclastogenesis depends on the presence or otherwise of other stimuli such as RANKL and possibly upon the maturation state of the OC precursors. It is proposed that the findings have particular relevance for the control of bone resorption in pathol
AB - Bone-resorbing osteoclasts (OCs) derive from macrophage lineage precursors under the potential control of many factors. Addition of macrophage-colony stimulating factor (M-CSF or CSF-1) to murine bone marrow cells gives rise to so-called bone marrow-derived macrophages (BMM); this adherent population can then be quantitatively converted into OC lineage cells when receptor activator of NF kappa B ligand (RANKL) is included. The effect of another CSF, granulocyte macrophage-CSF (GM-CSF), on OC differentiation in vitro is quite complex with both enhancing and suppressive actions being described. We report here that GM-CSF can generate a population of adherent macrophage lineage cells from murine bone marrow precursors (GM-BMM) which is also capable of giving rise to OC lineage cells in the presence of M-CSF and RANKL as effectively as BMM. The degree of this differentiation was surprising considering that GM-BMM are often referred to as immature dendritic cells and that, for both BMM and the GM-BMM, GM-CSF suppressed subsequent OC differentiation governed by M-CSF and RANKL. Unlike for BMM. this GM-CSF-mediated suppression for GM-BMM appeared to be independent of c-fibs expression. The effects on bone of another cytokine, transforming growth factor-beta (TGF-beta), are also quite complex although usually found to be stimulatory for OC differentiation. Unexpectedly, we observed that TGF-beta 1 also potently suppressed M-CSF+RANKL-driven OC differentiation from both BMM and GM-BMM. Using cells from gene-deficient mice, this inhibition of OC differentiation by both GM-CSF and TGF-beta 1 appeared to be independent of endogenous interferon alpha/beta production. It appears therefore that the influence of GM-CSF and TGF-beta on osteoclastogenesis depends on the presence or otherwise of other stimuli such as RANKL and possibly upon the maturation state of the OC precursors. It is proposed that the findings have particular relevance for the control of bone resorption in pathol
UR - http://www.sciencedirect.com/science/article/pii/S875632820600696X
U2 - 10.1016/j.bone.2006.09.003
DO - 10.1016/j.bone.2006.09.003
M3 - Article
SN - 8756-3282
VL - 40
SP - 323
EP - 336
JO - Bone
JF - Bone
IS - 2
ER -