ECTS Abstracts (2015) 1 P201

Osteoclastogenesis-insensitivity, a phenomenon that is induced by M-CSF priming and prevented when osteoclast precursors adhere to bone

Teun J de Vries1, Ton Schoenmaker1, David Aerts1, Pieter J M Leenen2 & Vincent Everts1

1ACTA, University of Amsterdam and VU University, Amsterdam, The Netherlands; 2Erasmus University, Rotterdam, The Netherlands.

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.

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