Figure 1.

Effects on osteoblasts. BPs can down-regulate “receptor activator of NF-κB ligand” (RANKL) and up-regulate osteoprotegerin (OPG) in osteoblasts, indicating indirect effects on the resorption. BPs can inhibit apoptosis of osteoblasts and osteocytes through Cx43 hemichannels. The opening of Cx43 hemichannels results in the activation of kinases, including Src and “extracellular signal-regulated kinases” (ERKs), which initiates the sequential phosphorylation of the ERK cytoplasmic target, p90RSK kinase, and final target substrates, BAD and C/EBPβ, thus suppressing apoptosis.