Unfolded protein response in osteoclastogenesis

Secreted proteins are synthesized and folded to acquire three-dimensional conformation in the endoplasmic reticulum(ER). Accumulation of unfolded proteins in the ER lumen triggers various cellular signals to remove these proteins and normalize the functions of the ER. This cellular mechanism is called the unfolded protein response(UPR)and medicated by three distinct signaling pathways in mammalian cells. Studies over the past decade have revealed that the UPR also has diverse functions that are not necessarily related to the maintenance of the ER. In osteoblasts and chondrocytes, it is now clear that the UPR not only functions to expand the capacity of the ER but also regulates the differentiation of these cells. Furthermore, recent studies suggest that the UPR is induced in osteoclast precursors after RANKL stimulation and has roles in osteoclastogenesis. This short review summarizes the findings of the recent studies on the unconventional roles of the UPR in osteoclast differentiation.