ArticleJournal of bone and mineral metabolism2013
Suppression of osteoclastogenesis through phosphorylation of eukaryotic translation initiation factor 2 alpha.
Article in Journal of bone and mineral metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases.Military Medical Research · 2023Review
- ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review.Biomolecules · 2023Review
- Proteomic evaluation of human osteoblast responses to titanium implants over time.Journal of biomedical materials research. Part A · 2023Article
- Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis.International journal of molecular sciences · 2021Article
- Dopamine D1 Receptor in Cancer.Cancers · 2020Review
- eIF2α signaling regulates autophagy of osteoblasts and the development of osteoclasts in OVX mice.Cell death & disease · 2019Article
- Pitavastatin slows tumor progression and alters urine-derived volatile organic compounds through the mevalonate pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Loss ofAmerican journal of physiology. Endocrinology and metabolism · 2019Article
- Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling.International journal of oncology · 2018Article
- Suppression of osteoclastogenesis via α2-adrenergic receptors.Biomedical reports · 2018Article
- GLUCOCORTICOID EXCESS IN BONE AND MUSCLE.Clinical reviews in bone and mineral metabolism · 2018Article
- Inhibiting checkpoint kinase 1 protects bone from bone resorption by mammary tumor in a mouse model.Oncotarget · 2018Article
- eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress.Scientific reports · 2017Article
- Role of endoplasmic reticulum stress pathway in hydrostatic pressure-induced apoptosis in rat mandibular condylar chondrocytes.Molecular and cellular biochemistry · 2017Article
- Inhibitory Effects of Dopamine Receptor DScientific reports · 2017Article
- Salubrinal Suppresses IL-17-Induced Upregulation of MMP-13 and Extracellular Matrix Degradation Through the NF-kB Pathway in Human Nucleus Pulposus Cells.Inflammation · 2016Article
- Article
- The unfolded protein response in skeletal development and homeostasis.Cellular and molecular life sciences : CMLS · 2016Review
- Tensile force on human macrophage cells promotes osteoclastogenesis through receptor activator of nuclear factor κB ligand induction.Journal of bone and mineral metabolism · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to various stresses including viral infection, nutrient deprivation, and stress to the endoplasmic reticulum, eukaryotic translation initiation factor 2 alpha (eIF2α) is phosphorylated to cope with stress induced apoptosis. Although bone cells are sensitive to environmental stresses that alter the phosphorylation level of eIF2α, little is known about the role of eIF2α mediated signaling during the development of bone-resorbing osteoclasts. Using two chemical agents (salubrinal and guanabenz) that selectively inhibit de-phosphorylation of eIF2α, we evaluated the effects of phosphorylation of eIF2α on osteoclastogenesis of RAW264.7 pre-osteoclasts as well as development of MC3T3 E1 osteoblast-like cells. The result showed that salubrinal and guanabenz stimulated matrix deposition of osteoblasts through upregulation of activating transcription factor 4 (ATF4). The result also revealed that these agents reduced expression of the nuclear factor of activated T cells c1 (NFATc1) and inhibited differentiation of RAW264.7 cells to multi-nucleated osteoclasts. Partial silencing of eIF2α with RNA interference reduced suppression of salubrinal/guanabenz-driven downregulation of NFATc1. Collectively, we demonstrated that the elevated phosphorylation level of eIF2α not only stimulates osteoblastogenesis but also inhibit osteoclastogenesis through regulation of ATF4 and NFATc1. The results suggest that eIF2α-mediated signaling might provide a novel therapeutic target for preventing bone loss in osteoporosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.