M-CSF Priming of Osteoclast Precursors Can Cause Osteoclastogenesis-Insensitivity, Which Can be Prevented and Overcome on Bone

T.J. de Vries, T. Schoenmaker, D. Aerts, L.C. Grevers, P.P.C. Souza, K. Nazmi, M.A. van de Wiel, B. Ylstra, P.L. van Lent, P.J.M. Leenen, V. Everts

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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; bone is likely the stimulus for osteoclast differentiation. To elucidate the effects of both, shared mouse bone marrow precursor myeloid blast was precultured with M-CSF on plastic and on bone. M-CSF priming prior to stimulation with M-CSF and osteoclast differentiation factor RANKL resulted in a complete loss of osteoclastogenic potential without bone. 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 osteoclast genes TRACP and DC-STAMP, 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 when bound to bone or when in the vicinity of bone.
Original languageEnglish
Pages (from-to)210-225
JournalJournal of Cellular Physiology
Volume230
Issue number1
DOIs
Publication statusPublished - 2015

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