RRC ID 71593
Author Lacey DL, Erdmann JM, Teitelbaum SL, Tan HL, Ohara J, Shioi A.
Title Interleukin 4, interferon-gamma, and prostaglandin E impact the osteoclastic cell-forming potential of murine bone marrow macrophages.
Journal Endocrinology
Abstract Interleukin 4 (IL-4) is an immune cytokine that inhibits bone resorption in mice and suppresses osteoclastic cell formation in vitro through an undefined mechanism. In this report, we have established the cellular identity of the IL-4 target cell using a variety of bone marrow/stromal cell coculture methods. Initially, we found that the majority of IL-4's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells, not stromal cells. Consequently, bone marrow macrophages were used as osteoclastic cell progenitors after they had been transiently exposed to IL-4 (48 h), before the addition of stromal cells, 1,25-dihydroxyvitamin D3, and dexamethasone. In this circumstance, IL-4 impaired subsequent osteoclastic cell formation, suggesting that the macrophage may be potentially targeted by many factors known to influence osteoclast formation. Consequently, we discovered that interferon-gamma (IFN gamma), prostaglandin E (PGE), and cell-permeant cAMP analogs also impacted osteoclastic cell formation when used to selectively treat bone marrow macrophages. IFN gamma suppressed osteoclastic cell formation, whereas PGE and cAMP analog treatment led to the formation of significantly enlarged osteoclastic cells. Importantly, PGE antagonized the inhibitory effects of both IL-4 and IFN gamma on the osteoclastic cell-forming potential of bone marrow macrophages. Collectively, these findings establish bone marrow macrophages as osteoclastic cell precursors with the degree of their commitment to the osteoclast pathway sensitive to the effects of soluble mediators, including IL-4, IFN gamma, and PGE.
Volume 136(6)
Pages 2367-76
Published 1995-6-1
DOI 10.1210/endo.136.6.7750457
PMID 7750457
MeSH Animals Bone Marrow / drug effects* Bone Marrow Cells* Bone Resorption / prevention & control Colony-Forming Units Assay Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / drug effects In Vitro Techniques Interferon-gamma / pharmacology* Interleukin-4 / pharmacology* Macrophages / cytology Macrophages / drug effects Mice Mice, Inbred C3H Models, Biological Osteoclasts / cytology Osteoclasts / drug effects Prostaglandins E / pharmacology*
IF 3.934
Human and Animal Cells ST2(RCB0224)