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Article Dans Une Revue Laboratory Investigation Année : 2019

Development of a simple osteoarthritis model useful to predict in vitro the anti-hypertrophic action of drugs

Résumé

Osteoarthritis (OA) is characterized by cartilage degradation, inflammation, and hypertrophy. Therapies are mainly symptomatic and aim to manage pain. Consequently, medical community is waiting for new treatments able to reduce OA process. This study aims to develop an in vitro simple OA model useful to predict drug ability to reduce cartilage hypertrophy. Human primary OA chondrocytes were incubated with transforming growth factor beta 1 (TGF-β1). Hypertrophy was evaluated by Runx2, type X collagen, MMP13, and VEGF expression. Cartilage anabolism was investigated by Sox9, aggrecan, type II collagen, and glycosaminoglycan expression. In chondrocytes, TGF-β1 increased expression of hypertrophic genes and activated canonical WNT pathway, while it decreased dramatically cartilage anabolism, suggesting that this treatment could mimic some OA features in vitro. Additionally, EZH2 inhibition, that has been previously reported to decrease cartilage hypertrophy and reduce OA development in vivo, attenuated COL10A1 and MMP13 upregulation and SOX9 downregulation induced by TGF-β1 treatment. Similarly, pterosin B (an inhibitor of Sik3), and DMOG (a hypoxia-inducible factor prolyl hydroxylase which mimicks hypoxia), repressed the expression of hypertrophy markers in TGF-β stimulated chondrocytes. In conclusion, we established an innovative OA model in vitro. This cheap and simple model will be useful to quickly screen new drugs with potential anti-arthritic effects, in complementary to current inflammatory models, and should permit to accelerate development of efficient treatments against OA able to reduce cartilage hypertrophy.
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Dates et versions

hal-02266635 , version 1 (15-08-2019)

Identifiants

Citer

Lyess Allas, Quitterie Rochoux, Sylvain Leclercq, Karim Boumediene, Catherine Baugé. Development of a simple osteoarthritis model useful to predict in vitro the anti-hypertrophic action of drugs. Laboratory Investigation, 2019, pp.64-71. ⟨10.1038/s41374-019-0303-0⟩. ⟨hal-02266635⟩
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