Osteoclasts and macrophages share progenitors that must receive decisive lineage signals driving them into their respective differentiation routes. Macrophage colony stimulation factor (M-CSF) is a common factor used for both lineages; bone is likely the stimulus for osteoclast differentiation. To elucidate the effect of both factors, mouse bone marrow precursor myeloid blasts were pre-cultured with M-CSF on plastic and on bone and the effect of osteoclast formation, gene and protein expression and bone resorption were assessed. M-CSF priming for three or four days prior to stimulation with M-CSF in combination with RANKL resulted in a complete loss of osteoclastogenic potential on tissue culture plastic. Such M-CSF primed cells expressed the receptor RANK, but lacked the crucial osteoclastogenic transcription factor NFATc1. This coincided with a steeply decreased expression of the osteoclast genes TRACP and DC-STAMP (p<0.05), but an increased expression of the macrophage markers F4/80 and CD11b. Compellingly, M-CSF priming on bone accelerated the osteoclastogenic potential: M-CSF primed cells that had received only one day M-CSF and RANKL and were grown on bone already expressed an array of genes that are associated with osteoclast differentiation and these cells differentiated into osteoclasts within 2 days. Osteoclastogenesis-insensitive precursors grown in the absence of bone regained their osteoclastogenic potential when transferred to bone. This implies that adhesion to bone dictates the fate of osteoclast precursors. Common macrophage-osteoclast precursors may become insensitive to differentiate into osteoclasts and regain osteoclastogenesis potential when in contact with or in the vicinity of bone.
Disclosure: The authors declared no competing interests.