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Journal Article Epublish 1 citation

PubMed: 42325870 DOI: 10.1016/j.ocarto.2026.100833

Evaluating therapeutic efficacy of iopanoic acid in a DMM-induced osteoarthritis mouse model and osteochondral lesioned human explants.

Osteoarthr Cartil Open 8(3):100833

Authors: S Sana Sayedipour, Giorgia Mazzini, Margo Tuerlings, Jelle Nikkels, Marijke Koedam, Luis J Cruz, Rachid Mahdad, Louise de Weerd, Bram van der Eerden, Yolande Fm Ramos, Ingrid Meulenbelt

Affiliations

  • Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Department Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, 3015 GD, Rotterdam, the Netherlands.
  • Department of Orthopaedics, Alrijne Hospital, Leiderdorp, the Netherlands.
  • Departments of Radiology & Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.

Abstract

OBJECTIVE

To evaluate the therapeutic potential of iopanoic acid (IOP), a thyroid hormone pathway inhibitor, in preserving cartilage and bone integrity in osteoarthritis (OA), using in vivo and ex vivo tissue models.

DESIGN

In the DMM mouse model, IOP was administered through intra-articular (i.a.) injection, either alone or combined with a thermosensitive hydrogel to enable sustained release. Histological analyses included damage, osteophyte, and synovitis scoring. Immunohistochemistry was performed for Col2, Mmp13, and CCDC80 to evaluate anabolic, catabolic, and hypertrophic markers. Micro-CT assessed subchondral bone changes. In the ex vivo studies, IOP was applied to lesioned human osteochondral OA explants. Matrix degradation and repair were evaluated by sulfated glycosaminoglycan (sGAG) release, Mankin histology scores, and RT-qPCR for cartilage matrix genes.

RESULTS

Administration of IOP significantly reduced cartilage degeneration in DMM mice, characterized by increased Col2, and decreased Mmp13 and CCDC80 expression. Notably, IOP also prevented pathological subchondral bone thickening. In human explants, IOP treatment led to a significant reduction in sGAG release compared to untreated explants on day 6 of the IOP treatment. Moreover, Mankin scores were significantly improved in IOP-treated compared to untreated explants, indicating reduced cartilage degradation.

CONCLUSION

IOP demonstrates strong chondroprotective effects, reducing cartilage degradation and promoting repair in OA models. Its combination with a thermosensitive hydrogel amplifies therapeutic potential, offering a promising strategy for OA treatment. Next steps are to optimize delivery and validate early molecular effects.

MeSH

Hydrogel, Polyethylene Glycol Dimethacrylate, Hydrogels, Iopanoic Acid, Osteoarthritis, Therapeutics, Cartilage