Receptor activator of nuclear factor kappa B ligand(RANKL) modulates the expression of genes involved in apoptosis and cell cycle in human osteoclasts.

ABSTRACTIt 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 momocytic/macrophagic lineage. However relatively little information is available on the ability of RANKLE 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 periferal blood mononuclear cells, which express the cognate high affinity receptor activator of nuclear factor kappa B (RANK), were differentiated alog 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 chemokine MIP1 alpha, which potentiates osteoclasic differentiation and simultaneously activated both antiapoptotic (Bcl-2) and pro-apoptotic (CIDEB, PYCARD, and BAK-1) genes. Moreover, RANKL markedly