Fig. 1

ZA inhibits the RANKL/RANK pathway. The RANKL is thought to bind with RANK, and their complex recruits TNF receptor-associated factors (TRAF6), activates phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mTOR pathway and subsequently nuclear factor kappa B (NF-κB) pathway, as well as nuclear factor of activation of T cells-1 (NFATc1), JNK, Erk and p38MAPK. ZA decreases the expression of RANKL to inhibit osteoclastogenesis, in addition, it is reported that ZA also inhibits NFATc1, suppresses NF-κB pathway, as well as inhibiting the phosphorylation of the nuclear translocation of p65, besides, ZA also inhibits non-canonical Wnt signaling through decreasing the signaling protein levels of Wnt5a, CaMKII, and the Ca2+ levels, and finally inhibits osteoclasts survival, proliferation, differentiation and apoptosis