ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review

作者：Wangli Huang, Yining Gong, Liang Yan · 发表于：Biomolecules · 年份：2023 · DOI：10.3390/biom13071050 · 被引用次数：61 · 研究领域：Endoplasmic Reticulum Stress and Disease、Alkaline Phosphatase Research Studies、Autophagy in Disease and Therapy

Endoplasmic reticulum (ER) stress and its adaptive mechanism, the unfolded protein response (UPR), are triggered by the accumulation of unfolded and misfolded proteins. During osteoclastogenesis, a large number of active proteins are synthesized. When an imbalance in the protein folding process occurs, it causes osteoclasts to trigger the UPR. This close association has led to the role of the UPR in osteoclastogenesis being increasingly explored. In recent years, several studies have reported the role of ER stress and UPR in osteoclastogenesis and bone resorption. Here, we reviewed the relevant literature and discussed the UPR signaling cascade response, osteoclastogenesis-related signaling pathways, and the role of UPR in osteoclastogenesis and bone resorption in detail. It was found that the UPR signal (PERK, CHOP, and IRE1-XBP1) promoted the expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL) in osteoblasts and indirectly enhanced osteoclastogenesis. IRE1 promoted osteoclastogenesis via promoting NF-κB, MAPK signaling, or the release of pro-inflammatory factors (IL-6, IL-1β, and TNFα). CREBH promoted osteoclast differentiation by promoting NFATc1 expression. The PERK signaling pathway also promoted osteoclastogenesis through NF-κB and MAPK signaling pathways, autophagy, and RANKL secretion from osteoblasts. However, salubrinal (an inhibitor of eIF2α dephosphorylation that upregulated p-eIF2α expression) directly inhibited osteoclastogenesis by...