ArticleArthritis research & therapy2006
The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein.
Article in Arthritis research & therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 41 citations in OpenAlex.
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- Design, Synthesis, and In Vitro Enzymatic Evaluation of Novel Flavone Derivatives as Dual COX-2/5-LOX Inhibitors Supported by Molecular Docking and ADMET Analysis.Current issues in molecular biology · 2026Article
- Neutrophil-initiated nociceptive ingrowth orchestrates inflammation resolution to potentiate bone regeneration.Bone research · 2026Article
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- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
- Development of multitarget agents possessing soluble epoxide hydrolase inhibitory activity.Prostaglandins & other lipid mediators · 2019Review
- Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration.Cell & bioscience · 2019Review
- Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level.The Eurasian journal of medicine · 2018Review
- Multitargeted Imidazoles: Potential Therapeutic Leads for Alzheimer's and Other Neurodegenerative Diseases.Journal of medicinal chemistry · 2017Article
- Inflammatory Eicosanoids Increase Amyloid Precursor Protein Expression via Activation of Multiple Neuronal Receptors.Scientific reports · 2015Article
- Dynamic model of eicosanoid production with special reference to non-steroidal anti-inflammatory drug-triggered hypersensitivity.IET systems biology · 2015Article
- Human articular chondrocytes express functional leukotriene B4 receptors.Journal of anatomy · 2015Article
- Inhibitors of the 5-lipoxygenase pathway activate pannexin1 channels in macrophages via the thromboxane receptor.American journal of physiology. Cell physiology · 2014Article
- Association of ADAMTS5 gene polymorphisms with osteoarthritis in Chinese Han population: a community-based case-control study.Rheumatology international · 2013Article
- Epithelium-dependent modulation of responsiveness of airways from caveolin-1 knockout mice is mediated through cyclooxygenase-2 and 5-lipoxygenase.British journal of pharmacology · 2012Article
- MATN3 gene polymorphism is associated with osteoarthritis in Chinese Han population: a community-based case-control study.TheScientificWorldJournal · 2012Article
- Strategy for NSAID administration to aspirin-intolerant asthmatics in combination with PGE2 analogue: a theoretical approach.Medical & biological engineering & computing · 2012Article
- Accelerated fracture healing in mice lacking the 5-lipoxygenase gene.Acta orthopaedica · 2010Article
- Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing.Pharmaceuticals (Basel, Switzerland) · 2010Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-beta (TGF-beta), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)2D3 and TGF-beta also modulated PGE2 production. TGF-beta stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-beta in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH)2D3 and TGF-beta depending on their endogenous low and high PGE2 levels.
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