ArticleCell death & disease2020
PERK controls bone homeostasis through the regulation of osteoclast differentiation and function.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 96 citations in OpenAlex.
- Clinical Effects of Lactobacillus reuteri on Gingival Inflammation and Alveolar Bone Loss in Periodontitis.Oral health & preventive dentistry · 2025Trial
- Necroptosis-related diseases are regulated by the unfolded protein response during endoplasmic reticulum stress.Genes & diseases · 2027Review
- Pharmacological investigation of bergapten isolated from Glehnia littoralis against periodontitis.Scientific reports · 2026Article
- Enhancing osteoporosis treatment: emerging roles of engineered exosomes in bone regeneration and repair.Journal of translational medicine · 2026Review
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- KLF10-IN-1 Attenuates RPE Cell Apoptosis and Experimental Diabetic Retinopathy Via the KLF10/PERK/eIF2α/ATF4/CHOP Pathway.Investigative ophthalmology & visual science · 2025Article
- Multifunctional metal-phenolic network coatings drive immunocompetent osseointegration via marrow microenvironment remodeling.Journal of nanobiotechnology · 2025Article
- Article
- Ferroptosis-mediated osteoclast-osteoblast crosstalk: signaling pathways governing bone remodeling in osteoporosis.Journal of orthopaedic surgery and research · 2025Review
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Phosphorylated protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression in breast cancer is correlated with malignant proliferation and histological grading.Histology and histopathology · 2025Article
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- Activation of the PERK Branch of the UPR as a Strategy for Improving Outcomes in Acute Ischemic Stroke.ACS omega · 2025Article
- Parkinson's Disease: The Neurodegenerative Enigma Under the "Undercurrent" of Endoplasmic Reticulum Stress.International journal of molecular sciences · 2025Review
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Beneficial effects of berberine in the treatment of diabetes and its complications.Frontiers in pharmacology · 2025Review
- Article
- Potential mechanism of gingerFrontiers in pharmacology · 2025Review
- Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding.Cellular and molecular life sciences : CMLS · 2024Article
- MiR-378 exaggerates angiogenesis and bone erosion in collagen-induced arthritis mice by regulating endoplasmic reticulum stress.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclasts are multinucleated giant cells with the ability to degrade bone tissue, and are closely related to abnormal bone metabolic diseases. Endoplasmic reticulum (ER) is an organelle responsible for protein modification, quality control, and transportation. The accumulation of unfolded or misfolded proteins in ER cavity induces ER stress. Double-stranded RNA-dependent protein kinase-like ER kinase (PERK) is an ER stress-sensing protein, which is ubiquitous in eukaryotic cells. Systemic PERK knockout mice show severe bone loss, suggesting that PERK is of great significance for maintaining the normal growth and development of bone tissue, but the role of PERK in osteoclastogenesis is still unclear. In this study, we found that PERK was significantly activated during RANKL-induced osteoclast differentiation; knockdown of PERK by siRNA and inhibition of PERK by GSK2606414, respectively, had significant negative regulatory effects on the formation and bone resorption of osteoclasts. PERK inhibitor GSK2606414 down-regulated the mRNA levels and protein expression of osteoclast differentiation marker genes, and inhibited RANKL-induced activation of Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Treatment with PERK inhibitor GSK2606414 in ovariectomized mouse model significantly suppressed bone loss and osteoclast formation. Thapsigargin activated ER stress to enhance autophagy, while GSK2606414 had a significant inhibitory effect on autophagy flux and autophagosome formation. Antioxidant N-acetylcysteine (NAC) could inhibit the expression of PERK phosphorylation, osteoclast-related proteins and autophagy-related proteins, but the use of PERK activator CCT020312 can reverse inhibition effect of NAC. Our findings demonstrate a key role for PERK in osteoclast differentiation and suggest its therapeutic potential.
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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 Socratic graph.