Fig. 1.

An overview of intracellular regulation of osteoclastogenesis and resorption activities. The early differentiation of myeloid progenitors to pOCs is mediated by M-CSF stimuli via PI3K/Akt and GRB2/ERK signaling. The binding of RANKL to RANK further promotes the differentiation of pOCs and activates intracellular TRAFs/NF-κB and TRAFs/MAPK signaling to increase transcription factors such as MYC, FOS, and NFATc1, upregulating the expression of osteoclast activation-related proteins and acid secretion. Phosphorylation of Plcγ2 by ITAM stimuli is also required for RANKL-induced NFATc1 activation.⁴⁶⁸ LGR4 activation can suppress RANKL-induced osteoclastogenesis via the GSK3β/MAPK pathway. Sema3A can inhibit ITAM-induced Plcγ2 activation and M-CSF-induced osteoclast differentiation through the RhoA signaling pathway