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RANKL binds to its receptor, namely, RANK, on osteoclast precursors and activates downstream signaling cascades, including nuclear factor kappa light chain enhancer of activated B cells (NF-B) and nuclear factor of activated T cells 1 (NFATc1), which promote precursor differentiation into mature, bone-resorbing osteoclasts and enhance their resorptive activity

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Although E2 has a stronger binding affinity than E3, unlike E2, E3 can accumulate in significant amounts in target organs to activate ER receptors [58, 59]