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Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Modulates the Expression of Genes Involved in Apoptosis and Cell Cycle in Human Osteoclasts
Author(s) -
Rimondi Erika,
Zweyer Marina,
Ricci Enrico,
Fadda Roberto,
Secchiero Paola
Publication year - 2007
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.20550
Subject(s) - rankl , microbiology and biotechnology , biology , rank ligand , activator (genetics) , macrophage colony stimulating factor , cancer research , receptor , macrophage , biochemistry , in vitro
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.