Identification of TGFbeta signatures in six murine models mimicking different osteoarthritis clinical phenotypes (Équipe Berenbaum)

14 - Juillet - 2020

M. Maumus, D. Noël, H.K. Ea, D. Moulin, M. Ruiz, E. Hay, X. Houard, D. Cleret, M. Cohen-Solal, C. Jacques, J.-Y. Jouzeau, M.-H. Lafage-Proust, P. Reboul, J. Sellam, C. Vinatier, F. Rannou, C. Jorgensen, J. Guicheux a, F. Berenbaum

Osteoarthritis Cartilage. 2020;28(10):1373-84

OBJECTIVE: TGFbeta is a key player in cartilage homeostasis and OA pathology. However, few data are available on the role of TGFbeta signalling in the different OA phenotypes. Here, we analysed the TGFbeta pathway by transcriptomic analysis in six mouse models of OA.

METHOD: We have brought together seven expert laboratories in OA pathophysiology and, used inter-laboratories standard operating procedures and quality controls to increase experimental reproducibility and decrease bias. As none of the available OA models covers the complexity and heterogeneity of the human disease, we used six different murine models of knee OA: from post-traumatic/mechanical models (meniscectomy (MNX), MNX and hypergravity (HG-MNX), MNX and high fat diet (HF-MNX), MNX and seipin knock-out (SP-MNX)) to aging-related OA and inflammatory OA (collagenase-induced OA (CIOA)). Four controls (MNX-sham, young, SP-sham, CIOA-sham) were added. OsteoArthritis Research Society International (OARSI)-based scoring of femoral condyles and ribonucleic acid (RNA) extraction from tibial plateau samples were done by single operators as well as the transcriptomic analysis of the TGFbeta family pathway by Custom TaqMan(R) Array Microfluidic Cards.

RESULTS: The transcriptomic analysis revealed specific gene signatures in each of the six models; however, no gene was deregulated in all six OA models. Of interest, we found that the combinatorial Gdf5-Cd36-Ltbp4 signature might discriminate distinct subgroups of OA: Cd36 upregulation is a hallmark of MNX-related OA while Gdf5 and Ltbp4 upregulation is related to MNX-induced OA and CIOA.

CONCLUSION: These findings stress the OA animal model heterogeneity and the need of caution when extrapolating results from one model to another.

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