Osteoarthritis

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Identify new molecules controlling osteo-articular joint destruction and repair

Identify new molecules controlling osteo-articular destruction in an inflammatory or mechanical context

The osteoarthritis project is centered on the molecular mechanisms of catabolic mediators (IL6) and the regeneration (Lin28a) of the cartilage. Our previous results show that IL6 exerts a catabolic role on cartilage and osteoarthritis, however, a systemic inhibition not relevant due to potential severe side effects. In order to identify more specific chondrocyte-specific downstream targets, we have conducted a transcriptomic high-throughput sequencing (RNAseq) analysis of the « whole genome » and identified several IL-6 target genes including CCL2 / CL7 chemokines and SerpinA3N. These candidate molecules will be analyzed at the mechanistic cell and tissue levels will be and integrated using KO mice before and after induction of joint instability. This project led by P. Richette is funded by industrial credits.

The second part will be focused on the regeneration of cartilage, in particular the mechanisms of cell reprogramming (Éric Hay). LIN28 is a post-transcriptional regulator of RNAs involved in pluripotency, differentiation and cell proliferation during development. The chondrocyte expression of Lin28 may be lost during aging and in osteoarthritis. We will analyze the reactivation capacity of Lin28 in senescent / osteoarthritic chondrocyte to induce cell reprogramming and allow the switch to a fully functional chondrocyte. For this purpose, mice with inducible conditional invalidation and overexpression of Lin28 will be subjected to experimental osteoarthritis. We will analyze the metabolic mechanisms at the origin of the programming. This project is supported by the Road network.

Expertise

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Researchers

HAY
Eric
MCU
RICHETTE
Pascal
PU PH
LATOURTE
Augustin
HU
COHEN-SOLAL
Martine
PU-PH
M Cossez-Guigne Thèse
M Hamroune M2
 
 

Publications

Al-Jazzar A, Javaheri B, Prideaux M, Boyde A, Scudamore CL, Cherifi C, Hay E, Hopkinson M, Boyd M, Cohen-Solal M, Farquharson C, Pitsillides AA. Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues. Int J Mol Sci. 2016 Dec 26;18(1)

Bouaziz W, Sigaux J, Modrowski D, Devignes C-S, Funck-Brentano T, Richette P, Ea HK, Provot S, Cohen-Solal M, Haÿ E Interaction of HIF1α and β-catenin inhibits matrix metalloproteinase 13 expression and prevents cartilage damage in mice. Proc Natl Acad Sci U S A [Internet]. 2016 May 10 [cited 2017 Jun 1];113(19):5453–8. Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1514854113

Haxaire C, Haÿ E, Geoffroy V. Runx2 controls bone resorption through the downregulation of the Wnt pathway in osteoblasts. Am J Pathol. 2016 Jun;186(6):1598-609. doi: 10.1016/j.ajpath.2016.01.016. Epub 2016 Apr 12.

Latourte A, Cherifi C, Maillet J, Ea HK, Bouaziz W, Funck-Brentano T, Cohen-Solal M, Hay E, Richette P. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann Rheum Dis. 2016 Oct 27

Bassiouni, Hassan; Aly, Hany; Zaky, Khaled; Abaza, Nouran; Bardin, Thomas. Probing The Relation Between Vitamin D Deficiency and Progression of Medial Femoro-tibial Osteoarthitis of the Knee. Current rheumatology reviews. 2017;13(1) :65-71

Bruyere, Olivier; Cooper, Cyrus; Arden, Nigel; Branco, Jaime; Brandi, Maria Luisa; Herrero-Beaumont, Gabriel; Berenbaum, Francis; Dennison, Elaine; Devogelaer, Jean-Pierre; Hochberg, Marc; Kanis, John; Laslop, Andrea; McAlindon, Tim; Reiter, Susanne; Richette, Pascal; Rizzoli, Rene; Reginster, Jean-Yves. Can We Identify Patients with High Risk of Osteoarthritis Progression Who Will Respond to Treatment? A Focus on Epidemiology and Phenotype of Osteoarthritis (vol 32, pg 179, 2015). DRUGS & AGING. 2017;34(5):411-411

Harvard, Stephanie; Guh, Daphne; Bansback, Nick; Richette, Pascal; Saraux, Alain; Fautrel, Bruno; Anis, Aslam H. Adherence to Antitumor Necrosis Factor Use Recommendations in Spondyloarthritis: Measurement and Effect in the DESIR Cohort. JOURNAL OF RHEUMATOLOGY. 2017;44(10):1436-1444

Richette, Pascal. Hyaluronic acid: Still useful in knee osteoarthritis? JOINT BONE SPINE. 2017;84(6):655-656

Latourte, Augustin; Soumare, Aicha; Bardin, Thomas; Perez-Ruiz, Fernando; Debette, Stephanie; Richette, Pascal. Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study.  Annals of the rheumatic diseases. 2018;77(3):328-335

Contacts

Osteoporosis

Martine
COHEN-SOLAL

+33 (0)1 49 95 86 42
martine.cohen-solal@inserm.fr

Tumor &
micro-environment

Dominique
MODROWSKI

+33 (0)1 49 95 63 52
dominique.modrowski@inserm.fr

Sylvain
PROVOT

+33 (0)1 49 95 64 02
sylvain.provot@inserm.fr

Osteoarthritis

Eric HAY

+33 (0)1 49 95 86 81
eric.hay@inserm.fr

Microcrystal & diseases

Korng
EA

+33 (0)1 49 95 63 57
korng.ea@inserm.fr