ArticleOxidative medicine and cellular longevity2019
4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Stress in Chondrocytes That Is Caused by Loss of the Protein Disulfide Isomerase ERp57.
Article in Oxidative medicine and cellular longevity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- 4-Phenylbutyrate mitigates renal pathology linked to ER stress related pathways in C57BL/6J mice with hindlimb unloading.Scientific reports · 2026Article
- Extracellular ERp57 promotes fibronectin fibril formation during matrix assembly of articular cartilage.iScience · 2025Article
- Impact of ER stress and the unfolded protein response on Fabry disease.EBioMedicine · 2025Review
- 4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model.Human molecular genetics · 2025Article
- Identification of Endoplasmic Reticulum Stress-Related Genes in Osteoporosis Pathogenesis.Mediators of inflammation · 2025Article
- Research progress on the cross-regulation between ferroptosis and immunogenic cell death in tumor micro-environment.Frontiers in oncology · 2025Review
- Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia.Nature communications · 2023Article
- Loss of surface transport is a main cellular pathomechanism of CRB2 variants causing podocytopathies.Life science alliance · 2023Article
- The clusterin connectome: Emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis.Frontiers in immunology · 2023Article
- Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.American journal of physiology. Cell physiology · 2023Article
- Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.iScience · 2022Article
- 4-Phenylbutyrate Mitigates the Motor Impairment and Dopaminergic Neuronal Death During Parkinson's Disease Pathology via Targeting VDAC1 Mediated Mitochondrial Function and Astrocytes Activation.Neurochemical research · 2022Article
- TGFβ1 regulates HRas-mediated activation of IRE1α through the PERK-RPAP2 axis in keratinocytes.Molecular carcinogenesis · 2022Article
- Potential Methods of Targeting Cellular Aging Hallmarks to Reverse Osteoarthritic Phenotype of Chondrocytes.Biology · 2022Review
- Endoplasmic reticulum stress is involved in lipid accumulation induced by oleic acid in adipocytes of grass carp (Ctenopharyngodon idella): focusing on the transcriptional level.Fish physiology and biochemistry · 2022Article
- Estradiol Inhibits ER Stress-Induced Apoptosis in Chondrocytes and Contributes to a Reduced Osteoarthritic Cartilage Degeneration in Female Mice.Frontiers in cell and developmental biology · 2022Article
- Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease.Frontiers in aging · 2022Review
- ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation.International journal of molecular sciences · 2021Article
- Sodium phenylbutyrate reduces repetitive self-grooming behavior and rescues social and cognitive deficits in mouse models of autism.Psychopharmacology · 2021Article
- mtROS InducedFrontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe integrity of cartilage depends on the correct synthesis of extracellular matrix (ECM) components. In case of insufficient folding of proteins in the endoplasmic reticulum (ER) of chondrocytes, ECM proteins aggregate, ER stress evolves, and the unfolded protein response (UPR) is initiated. By this mechanism, chondrocytes relieve the stress condition or initiate cell death by apoptosis. Especially persistent ER stress has emerged as a pathogenic mechanism in cartilage diseases, such as chondrodysplasias and osteoarthritis. As pharmacological intervention is not available yet, it is of great interest to understand cartilage ER stress in detail and to develop therapeutics to intervene.
methodsERp57-deficient chondrocytes were generated by CRISPR/Cas9-induced KO. ER stress and autophagy were studied on mRNA and protein level as well as by transmission electron microscopy (TEM) in chondrocyte micromass or cartilage explant cultures of ERp57 KO mice. Thapsigargin (Tg), an inhibitor of the ER-residing Ca
resultsOur data reveal that the loss of the protein disulfide isomerase ERp57 is sufficient to induce ER stress in chondrocytes. 4-PBA efficiently diffuses into cartilage explant cultures and diminishes excessive ER stress in chondrocytes dose dependently, no matter if it is induced by ERp57 KO or stimulation with Tg.
conclusionER-stress-related diseases have different sources; therefore, various targets for therapeutic treatment exist. In the future, 4-PBA may be used alone or in combination with other drugs for the treatment of ER-stress-related skeletal disorders in patients.
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