{
  "abstract": "Objective: Persistent extracellular prostaglandin signaling contributes to synovial inflammation and pain in osteoarthritis (OA), although prostaglandin E2 (PGE2) can also have context-dependent homeostatic functions. Decanoic acid (DA) is a 10-carbon medium-chain fatty acid with reported peroxisome proliferator-activated receptor-modulating and anti-inflammatory activity. Its amphipathic carboxylate structure also made it an exploratory candidate for interaction with the hydrophobic organic-anion binding region of multidrug resistance protein 4 (MRP4/ABCC4). We tested whether DA changes prostaglandin compartmentalization and enhances the effect of very-low-dose dexamethasone (Dex) in interleukin-1β (IL-1β)-stimulated human OA fibroblast-like synoviocytes.\n\nMethods: Primary human osteoarthritis fibroblast-like synoviocytes were stimulated with IL-1β and treated with DA, Dex, or their combination. Extracellular and intracellular prostaglandins were quantified by competitive ELISA. MRP4 inhibition was evaluated in inside-out HEK293 membrane vesicles overexpressing human MRP4 using ATP-dependent DHEAS transport, with MK-571 as the positive inhibitor control. Molecular docking and UHPLC-MS lipidomics were also performed. Replicates were independently cultured wells or pellets from the same donor\n\nResults: DA reduced extracellular PGE2 and increased intracellular PGE2. With a fixed 0.1 nM Dex background, the fitted DA IC50 changed from 19.42 μM (95% CI, 11.14–32.49 μM) to 8.62 μM (95% CI, 4.69–15.26 μM) with an F-test P = 0.0402, indicating Das ability to potentiate the inhibitory effect of sub-nanomolar DEX. DA also reduced extracellular PGD2 and PGI2. In vesicles, DA inhibited MRP4-mediated DHEAS transport in a concentration-dependent manner (calculated IC50, approximately 33.86 μM), but PGE2 transport was not measured directly. Docking placed DA near the MK-571 reference pose. DA was also associated with increased 17(S)-HDHA and maresin 2 (MaR2).\n\nConclusions: In this single-donor proof-of-concept model, DA altered prostaglandin distribution, inhibited MRP4 probe-substrate transport, and enhanced extracellular prostaglandin suppression in the presence of low-dose Dex. The findings are consistent with, but do not prove, an MRP4-associated contribution to prostaglandin export. The increases in 17(S)-HDHA and MaR2 are associative and do not establish that intracellular PGE2 retention caused resolution signaling. Multi-donor validation, direct PGE2 transport studies, genetic MRP4 experiments, and intra-articular pharmacokinetic and safety studies are required.",
  "abstract_shown": true,
  "affiliations": [
    "Trauma Research, Swedish Medical Center , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jason Williams"
    },
    {
      "affs": [
        0
      ],
      "name": "Melissa A. Hausburg"
    },
    {
      "affs": [
        0
      ],
      "name": "Gregory W. Thomas"
    },
    {
      "affs": [
        0
      ],
      "name": "Raphael Bar-Or"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaysie Banton"
    },
    {
      "affs": [
        0
      ],
      "name": "David Bar-Or"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0t4cx93j83y95.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1876378",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727426/?tool=EBI",
  "id": "0t4cx93j83y95",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13727426",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7223015369",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727426/pdf/?tool=EBI",
  "pmcid": "PMC13727426",
  "pmid": "42978558",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0t4cx93j83y95.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13727426",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727426"
    },
    {
      "first_seen": "2026-11-06T12:23:18Z",
      "native_id": "PMC13727426",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmed.2026.1876378"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Decanoic acid reduces extracellular prostaglandin accumulation, inhibits MRP4 transport, and enhances low-dose dexamethasone effects in IL-1β-stimulated human osteoarthritis synoviocytes",
  "title_text": "Decanoic acid reduces extracellular prostaglandin accumulation, inhibits MRP4 transport, and enhances low-dose dexamethasone effects in IL-1β-stimulated human osteoarthritis synoviocytes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:36Z",
  "url": "https://research.draconitic.com/paper/0t4cx93j83y95",
  "venue": "Frontiers in medicine",
  "versions": []
}