Macrophage lineage phenotypes and osteoclastogenesis-Complexity in the control by GM-CSF and TGF-beta

Roya Lari, Andrew J Fleetwood, Peter D Kitchener, Andrew D Cook, Durda Pavasovic, Paul John Hertzog, J Hamilton

Research output: Contribution to journalArticleResearchpeer-review

70 Citations (Scopus)


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
Original languageEnglish
Pages (from-to)323 - 336
Number of pages14
Issue number2
Publication statusPublished - 2007

Cite this