Receptor activator of nuclear factor kappa B ligand (RANKL) modulates the expression of genes involved in apoptosis and cell cycle in human osteoclasts.
It has been clearly established that receptor activator of nuclear factor kappa B ligand (RANKL) is a key cytokine involved in the differentiation of osteoclastic precursors of the monocytic/macrophagic lineage. However, relatively little information is available on the ability of RANKL to modulate the expression of genes controlling cell survival/apoptosis and proliferation in human osteoclastic cells in comparison to macrophages. For this purpose, CD14+ human peripheral blood mononuclear cells, which express the cognate high affinity receptor activator of nuclear factor kappa B (RANK), were differentiated along the macrophagic or osteoclastic lineage by adding macrophage-colony stimulating factor (M-CSF) or M-CSF plus RANKL in culture for 12 days. RANKL up-regulated the expression of the chemokine MIP1alpha, which potentiates osteoclastic differentiation and simultaneously activated both anti-apoptotic (Bcl-2) and pro-apoptotic (CIDEB, PYCARD, and BAK-1) genes. Moreover, RANKL markedly up-regulated cylin D2, while it significantly decreased the levels of cyclin A, cyclin-dependent kinase 2, and other cyclin-dependent kinases, in keeping with the notion that end-stage osteoclasts are nondividing cells. Finally, a long-term exposure of RANKL up-regulated the adaptor protein TRAF3 but not TRAF6.
Rimondi
Erika
E
Department of Morphology and Embryology, Human Anatomy Section,University of Ferrara, Ferrara, Italy.
Zweyer
Marina
M
Ricci
Enrico
E
Fadda
Roberto
R
Secchiero
Paola
P
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000276:immunology / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D039481:CD11b Antigen; D018797:Cell Cycle Proteins; D016207:Cytokines; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D053245:RANK Ligand; D012333:RNA, Messenger; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor