Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Modulates the Expression of Genes Involved in Apoptosis and Cell Cycle in Human Osteoclasts

✍ Scribed by Erika Rimondi; Marina Zweyer; Enrico Ricci; Roberto Fadda; Paola Secchiero

• Publisher: Wiley (John Wiley & Sons)
• Year: 2007
• Tongue: English
• Weight: 307 KB
• Volume: 290
• Category: Article
• ISSN: 1932-8486
• DOI: 10.1002/ar.20550

✦ Synopsis

Abstract

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 MIP1α, 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. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc.