A selective c-Fos/AP-1 inhibitor prevents cartilage destruction and subsequent osteophyte formation

Biochemical and Biophysical Research Communications
Hiraku MotomuraTomoatsu Kimura

Abstract

The objective of the present study is to demonstrate that a newly developed selective c-Fos/activator protein (AP)-1 inhibitor, T-5224, inhibits the expression of matrix metalloproteinases (MMPs) in human articular chondrocytes, and prevents cartilage destruction in an osteoarthritis (OA)-induced mouse model. First, we examined the effect of T-5224 on MMP and inflammatory cytokine expression by real-time polymerase chain reaction in human articular chondrocytes. We created an OA model by destabilization of the medial meniscus (DMM) in mice. T-5224 was orally administered once a day and the OA pathology was assessed by histological, immunohistochemical, and micro-computed tomography (CT) analyses. T-5224 inhibited the mRNA expression levels of MMP-1, 3, and 13, and interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in IL-1-stimulated human chondrocytes. Oral administration of T-5224 to OA-induced mice prevented cartilage destruction. The histological scores for OA were significantly better in the T-5224-treated group than the vehicle-treated group. Type X collagen and MMP-13 were not increased in the T-5224-treated group by immunohistochemical staining. Micro-CT analysis showed mild but apparent osteophyte development i...Continue Reading

Citations

Nov 22, 2018·Clinical and Translational Medicine·Santul BapatSadanand Fulzele
Sep 18, 2020·Biology·Margot NeefjesPeter M van der Kraan
Feb 2, 2019·World Journal of Surgical Oncology·Cheng XiaoZhen Liu
Apr 30, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Fabienne BejjaniIsabelle Jariel-Encontre
Jul 25, 2021·International Journal of Molecular Sciences·Constanze BuhrmannMehdi Shakibaei
Jun 14, 2018·Biochemistry·Evert NjomenJetze J Tepe

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