Open AccessPERK signaling pathway in bone metabolism: Friend or foe?
Author(s) -
Guo Jiachao,
Ren Ranyue,
Sun Kai,
He Jinpeng,
Shao Jingfan
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13011
Subject(s) - bone remodeling , endoplasmic reticulum , microbiology and biotechnology , unfolded protein response , signal transduction , osteoblast , kinase , protein kinase a , osteoclast , intracellular , biology , eif 2 kinase , endocrinology , biochemistry , receptor , in vitro , cyclin dependent kinase 2
Abstract Osteoblasts and osteoclasts participate in the process of bone remodelling to meet the needs of normal growth and development or repair pathological damage. Endoplasmic reticulum stress (ER stress) can break the intracellular homeostasis of osteoclasts and osteoblasts, which is closely related to abnormal bone remodelling. The double‐stranded RNA‐dependent protein kinase (PKR)‐like ER kinase (PERK) is a key transmembrane protein that regulates ER stress, and growing evidence suggests that the PERK pathway plays a crucial role in regulating bone metabolism under both physiological and pathological conditions. Based on the current findings, we summarized the main mechanisms involved in bone metabolism downstream of the PERK pathway, among which elF2α, FOXO1, CaN, Nrf2 and DAG play a role in regulating the differentiation of osteoblasts and osteoclasts. Importantly, strategies by the regulation of PERK pathway exert beneficial effects in preclinical trials of several bone‐related diseases. Given the importance and novelty of PERK pathway, we provide an overview and discuss the roles of PERK pathway in regulating bone metabolism and its impact on bone‐related diseases. We hope that the development of research in this field will bring a bright future for the treatment of bone‐related diseases.