Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Prolif. 2021 Apr;54(4):e13011. doi: 10.1111/cpr.13011. Epub 2021 Feb 21.
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.
成骨细胞和破骨细胞参与骨重建过程，以满足正常生长发育或修复病理损伤的需要。内质网应激（ER 应激）可破坏破骨细胞和成骨细胞的细胞内稳态，与异常骨重建密切相关。双链 RNA 依赖性蛋白激酶（PKR）样 ER 激酶（PERK）是一种调节 ER 应激的关键跨膜蛋白，越来越多的证据表明，PERK 途径在生理和病理条件下调节骨代谢中起着至关重要的作用。基于目前的研究结果，我们总结了 PERK 途径下游骨代谢的主要机制，其中 eIF2α、FOXO1、CaN、Nrf2 和 DAG 在调节成骨细胞和破骨细胞的分化中发挥作用。重要的是，PERK 途径的调节策略在几种与骨相关疾病的临床前试验中发挥了有益的作用。鉴于 PERK 途径的重要性和新颖性，我们提供了概述并讨论了 PERK 途径在调节骨代谢及其对与骨相关疾病的影响中的作用。我们希望该领域研究的发展将为治疗与骨相关的疾病带来光明的未来。
