Major cytokines in the bone microenvironment that regulate OC function. Stimulatory factors are shown in orange and inhibitory factors are shown in blue. Positive (+) or negative (–) effects of E on these regulatory factors are shown in red. The blow-up circle shows that TNF-α and RANKL act through separate receptors, but both activate the NF-κB and JNK intracellular signaling pathways. GM-CSF, granulocyte macrophage-colony-stimulating factor.