ArticleFrontiers in endocrinology2014
Deletion of P58(IPK), the Cellular Inhibitor of the Protein Kinases PKR and PERK, Causes Bone Changes and Joint Degeneration in Mice.
Article in Frontiers in endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Meta-analysis Integrated With Multi-omics Data Analysis to Elucidate Pathogenic Mechanisms of Age-Related Knee Osteoarthritis in Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Pooled it
- Mitochondrial dysfunction activates ADAMTS-5 expression via mt-dsRNA-PKR-Spi-1 axis in osteoarthritic chondrocytes.iScience · 2026Article
- Evaluating Knee Osteoarthritis Induction Methods in Small Translational Animal Models from 1970-2025: A Comprehensive Systematic Review.The archives of bone and joint surgery · 2026Review
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Obesity-induced NLRP3 inflammasome activation in nucleus pulposus cells accelerates intervertebral disk degeneration.Journal of orthopaedic surgery and research · 2025Article
- Osteoking promotes bone formation and bone defect repair through ZBP1-STAT1-PKR-MLKL-mediated necroptosis.Chinese medicine · 2024Article
- Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms.Biochemistry and biophysics reports · 2022Article
- Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage.International journal of molecular sciences · 2021Review
- Typical Stress Granule Proteins Interact with the 3' Untranslated Region of Enterovirus D68 To Inhibit Viral Replication.Journal of virology · 2020Article
- Long noncoding RNA DNAJC3-AS1 promotes osteosarcoma progression via its sense-cognate gene DNAJC3.Cancer medicine · 2019Article
- Curcumin Inhibits the PERK-eIF2Oxidative medicine and cellular longevity · 2019Article
- PERK-mediated translational control is required for collagen secretion in chondrocytes.Scientific reports · 2018Article
- Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveProtein kinase-like endoplasmic reticulum kinase (PERK) and protein kinase R (PKR) are implicated in endoplasmic reticulum stress-induced arthritis and pro-inflammatory cytokine-mediated cartilage degradation in vitro, respectively. We determined whether knockout of the cellular inhibitor of PERK and PKR, P58(IPK) causes joint degeneration in vivo and whether these molecules are activated in human osteoarthritis (OA). MATERIALS AND
methodsSections of knee joints from P58(IPK)-null and wild-type mice aged 12-13 and 23-25 months were stained with toluidine blue and scored for degeneration using the osteoarthritis research society international (OARSI) system. Bone changes were assessed by radiology and high-resolution micro-computed tomography of hind limbs. Sections from the medial tibial plateaus of two human knees, removed in total knee replacement surgery for OA, were immunolabelled for phosphorylated PERK and PKR and P58(IPK).
resultsKnockout mice exhibited narrower tibiae (p = 0.0031) and smaller epiphyses in tibiae (p = 0.0004) and femora (p = 0.0214). Older knockout mice had reduced total volume inside the femoral periosteal envelope (p = 0.023), reduced tibial (p = 0.03), and femoral (p = 0.0012) bone volumes (BV) and reduced femoral BV fraction (p = 0.025). Compared with wild-types, younger P58(IPK)-null mice had increased OARSI scores in medial femoral condyles (p = 0.035). Thirty four percent of null mice displayed severe joint degeneration with complete articular cartilage loss from the medial compartment and heterotopic chondro-osseous tissue in the medial joint capsule. Phosphorylated PERK and PKR were localized throughout human osteoarthritic tibial plateaus but, in particular, in areas exhibiting the most degeneration. There was limited expression of P58(IPK).
conclusionThis study is the first to reveal a critical role for P58(IPK) in maintaining joint integrity in vivo, implicating the PKR and PERK stress signaling pathways in bony changes underlying the pathogenesis of joint degeneration.
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