Enhancement of osteoblastogenesis and suppression of osteoclastogenesis by inhibition of de-phosphorylation of eukaryotic translation initiation factor 2 alpha

Abstract

The phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2a) is activated in response to various stresses such as viral infection, nutrient deprivation, and stress to the endoplasmic reticulum. Severe stress to the endoplasmic reticulum, for instance, induces an apoptotic pathway, while mild stress, on the contrary, leads to a pro-survival pathway. Little has been known about the elaborate role of eIF2a phosphorylation in the development of bone-forming osteoblasts and bone-resorbing osteoclasts. Using salubrinal and guanabenz as inhibitors of the de-phosphorylation of eIF2a, we have recently reported that the phosphorylation of eIF2a significantly alters fates of both osteoblasts and osteoclasts. Based on our recent findings, we review in this research highlight the potential mechanisms of the enhancement of osteoblastogenesis and the suppression of osteoclastogenesis through the elevated level of phosphorylated eIF2a.