De Vries Teun J, Schoenmaker Ton, Aerts David, Grevers Lilyanne C, Souza Pedro P C, Nazmi Kamran, van de Wiel Mark, Ylstra Bauke, Lent Peter L Van, Leenen Pieter J M, Everts Vincent
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.
J Cell Physiol. 2015 Jan;230(1):210-25. doi: 10.1002/jcp.24702.
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.
破骨细胞和巨噬细胞拥有共同的祖细胞，这些祖细胞必须接收决定性的谱系信号，从而驱动它们进入各自的分化途径。巨噬细胞集落刺激因子M-CSF是一个共同因素；骨骼可能是破骨细胞分化的刺激因素。为了阐明这两者的作用，将共有的小鼠骨髓前体髓系母细胞与M-CSF在塑料和骨上进行预培养。在用M-CSF和破骨细胞分化因子RANKL刺激之前进行M-CSF预处理，导致在没有骨的情况下破骨细胞生成潜能完全丧失。这种经M-CSF预处理的细胞表达受体RANK，但缺乏关键的破骨细胞生成转录因子NFATc1。这与破骨细胞基因TRACP和DC-STAMP的表达急剧下降，但巨噬细胞标志物F4/80和CD11b的表达增加相一致。引人注目的是，在骨上进行M-CSF预处理可加速破骨细胞生成潜能：仅接受一天M-CSF和RANKL并在骨上生长的经M-CSF预处理的细胞已经表达了一系列与破骨细胞分化相关的基因，并且这些细胞在2天内分化为破骨细胞。在没有骨的情况下生长的对破骨细胞生成不敏感的前体，当转移到骨上时恢复了它们的破骨细胞生成潜能。这意味着与骨的粘附决定了破骨细胞前体的命运。常见的巨噬细胞-破骨细胞前体可能会变得对分化为破骨细胞不敏感，并在与骨结合或在骨附近时恢复破骨细胞生成能力。
