title: M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone.
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 effect of both, shared mouse bone marrow precursor myeloid blast was pre-cultured 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.
authors: Department of Periodontology, University of Amsterdam VU University, MOVE Research Institute, Amsterdam, The Netherlands; Department of Oral Cell Biology, University of Amsterdam VU University, MOVE Research Institute, Amsterdam, The Netherlands.
authors: Teun J
authors: TJ
authors: De Vries
authors: Ton
authors: T
authors: Schoenmaker
authors: David
authors: D
authors: Aerts
authors: Lilyanne C
authors: LC
authors: Grevers
authors: Pedro P C
authors: PP
authors: Souza
authors: Kamran
authors: K
authors: Nazmi
authors: Mark
authors: M
authors: van de Wiel
authors: Bauke
authors: B
authors: Ylstra
authors: Peter L Van
authors: PL
authors: Lent
authors: Pieter J M
authors: PJ
authors: Leenen
authors: Vincent
authors: V
authors: Everts
mesh_terms: D000135:Acid Phosphatase / Q000096:biosynthesis; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D007527:Isoenzymes / Q000096:biosynthesis; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D053245:RANK Ligand / Q000494:pharmacology*; D013234:Stem Cells; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; C499636:DC-STAMP protein, mouse; D007527:Isoenzymes; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; C036763:monocyte-macrophage differentiation antigen; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase