ArticleCell death and differentiation2010
Prostaglandin (PG)D(2) and 15-deoxy-Delta(12,14)-PGJ(2), but not PGE(2), mediate shear-induced chondrocyte apoptosis via protein kinase A-dependent regulation of polo-like kinases.
Article in Cell death and differentiation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Harnessing bi-exosome combination alleviates osteoarthritis progression.Bioactive materials · 2026Article
- CMKLR1/PKA signaling reinforces sonic hedgehog pathway to promote medulloblastoma pathogenesis.Oncogenesis · 2025Article
- Quantitative phosphoproteomic analysis reveals unique cAMP signaling pools emanating from AC2 and AC6 in human airway smooth muscle cells.Frontiers in physiology · 2023Article
- Identification and comprehensive analysis of circRNA-miRNA-mRNA regulatory networks in osteoarthritis.Frontiers in immunology · 2022Article
- Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis.Biomolecules · 2020Review
- 15-Deoxy-ΔDrug design, development and therapy · 2019Review
- Comparative proteome analysis of abdominal adipose tissues between fat and lean broilers.Proteome science · 2016Article
- Lubricin restoration in a mouse model of congenital deficiency.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways.Oncogene · 2015Article
- Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition.Oncotarget · 2014Article
- Fluid shear stress-induced osteoarthritis: roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Review
- Prostaglandin D2 toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites.Neurotoxicology · 2013Article
- Notch4-dependent antagonism of canonical TGF-β1 signaling defines unique temporal fluctuations of SMAD3 activity in sheared proximal tubular epithelial cells.American journal of physiology. Renal physiology · 2013Article
- Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation.Scientific reports · 2013Article
- Epithelial-mesenchymal transition and fibrosis are mutually exclusive reponses in shear-activated proximal tubular epithelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- The antagonistic actions of endogenous interleukin-1β and 15-deoxy-Δ12,14-prostaglandin J2 regulate the temporal synthesis of matrix metalloproteinase-9 in sheared chondrocytes.The Journal of biological chemistry · 2012Article
- Cardiac-generated prostanoids mediate cardiac myocyte apoptosis after myocardial ischaemia.Cardiovascular research · 2012Article
- Loss of giant obscurins promotes breast epithelial cell survival through apoptotic resistance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Prostaglandins and rheumatoid arthritis.Arthritis · 2012Article
- Response of chondrocytes to shear stress: antagonistic effects of the binding partners Toll-like receptor 4 and caveolin-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Excessive mechanical loading of cartilage producing hydrostatic stress, tensile strain and fluid flow leads to chondrocyte apoptosis and osteoarthritis. High fluid flow induces cyclooxygenase-2 (COX-2) expression in sheared chondrocytes, which suppresses their antioxidant capacity and contributes to apoptosis. The pivotal role of COX-2 in shear-induced chondrocyte apoptosis and the conflicting literature data on the roles of prostaglandin (PG)E(2), PGD(2) and its metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in chondrocyte apoptosis prompted us to analyze which COX-2-derived PG is involved in this process. We show that exogenously added PGD(2) and 15d-PGJ(2), but not PGE(2), diminish the viability of human T/C-28a2 chondrocytes under static conditions. In agreement with these observations, knockdown of L-PGD synthase (L-PGDS) abolishes shear-induced chondrocyte apoptosis. Using cDNA microarrays in conjunction with clustering algorithms, we propose a novel signaling pathway by which high fluid shear mediates COX-2/L-PGDS-dependent chondrocyte apoptosis, which is validated by molecular interventions. We show that L-PGDS controls the downregulation of protein kinase A (PKA), which in turn regulates Polo-like kinase1 (Plk1) and Plk3. Plks target p53, which controls the transcription of p53 effectors (TP53INPs, FAS and Bax) involved in chondrocyte apoptosis. Reconstructing the signaling network regulating chondrocyte apoptosis may provide insights to optimize conditions for culturing artificial cartilage in bioreactors and for developing therapeutic strategies for arthritic disorders.
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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 OpenQuestion graph.