Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8297689 | Biochemical and Biophysical Research Communications | 2013 | 6 Pages |
Abstract
Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process. These findings provide a better understanding of the role of IL-3 in osteoclastogenesis.
Keywords
HSCcommon myeloid progenitorsCarbonic anhydrase 2Osteoclast precursorCTSKIL-3M-CSFMMP9SCFGM-CSFα-MEMCMPTRAPAPCGMPBRCFBSIL-6PBSBMCGAPDHRANKLRT-PCRMSCgranulocyte/macrophage colony stimulating factorα-Minimal essential mediumallophycocyaninOsteoclastogenesisTartrate resistant acid phosphataseInterleukin 3interleukin 6Interleukin-3fetal bovine serumhematopoietic stem cellsMesenchymal stem cellsBone marrow cellsStem Cell FactorphycoerythrinMatrix metalloproteinase 9SEMScanning electron microscopyreverse transcription-polymerase chain reactionCathepsin Kglyceraldehyde 3-phosphate dehydrogenasereceptor activator of nuclear factor kappa B ligand
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Authors
Huixian Hong, Zhenqi Shi, Ping Qiao, Hui Li, Erin M. McCoy, Ping Mao, Hui Xu, Xu Feng, Shunqing Wang,