{"id":1917,"date":"2017-07-21T13:10:01","date_gmt":"2017-07-21T11:10:01","guid":{"rendered":"http:\/\/lbti.ibcp.fr\/?page_id=1917"},"modified":"2024-05-29T10:33:17","modified_gmt":"2024-05-29T08:33:17","slug":"voies-de-signalisation-sous-controle-de-lhypoxie-condition-physiologique-du-cartilage","status":"publish","type":"page","link":"https:\/\/lbti.ibcp.fr\/?page_id=1917","title":{"rendered":"Epigenetics during osteoarthritis"},"content":{"rendered":"

Project leader<\/strong><\/em> : J\u00e9r\u00f4me Lafont<\/a><\/strong><\/span><\/h4>\n

Participants\u00a0\u00a0<\/strong><\/em>: F. Mallein-Gerin, M. Pasdeloup, S. Moustaghfir<\/span><\/p>\n

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Although many epigenetic modifications have been described during osteoarthritis (OA), the precise contribution of the chromatin remodeling enzymes during OA is still unclear. The histone demethylase LSD-1 (Lysine-Specific-Demethylase-1) is up-regulated in OA joints and induces the expression of inflammatory molecules such as mPges-1. We found that LSD1 downregulates the COL9A1 gene, which encodes a structural protein of the cartilage collagen fibrils (the type IX collagen) synthesised by articular chondrocytes. These results suggest that LSD1 plays an important role in articular cartilage, notably as a potential promoter of OA. Thus we study the LSD-1 mediated epigenetic signaling in the context of cartilage homeostasis and test the inhibition of LSD-1 as a strategy to prevent OA.<\/p>\n

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We use Tamoxifen-inducible conditional knockout (cKO) mice to invalidate Lsd-1 specially in chondrocytes (Col2a1-CreERT: lsd-1fl\/fl) to evaluate the impact of the absence of Lsd-1 on OA development. Various technics (IHC, FISH qPCR etc…) are used to characterise the joints and to evaluate the OA progression in post-traumatic OA (surgically-induced). The mechanisms (epigenetic signaling) by which catabolic\/anabolic genes are regulated by LSD-1 are also investigated through in vitro <\/em>approaches.<\/p>\n

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Left<\/strong>: structural analysis of LSD-1 (PyMol) highlights the potential site for protein-protein interactions (histone and non-histone). Right<\/strong>: safranin-o staining of knee joint section of sham vs. surgically-induced OA mice (DMM).<\/p>\n<\/div>\n

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Selected publications :\u00a0<\/strong><\/em><\/span><\/p>\n

1. Lafont JE<\/b>, Moustaghfir S, Durand AL, Mallein-Gerin F. The epigenetic players and the chromatin marks involved in the articular cartilage during osteoarthritis.<\/a> Front Physiol.<\/strong> 2023 Jan 17;14:1070241. doi: 10.3389\/fphys.2023.1070241. eCollection 2023.<\/span> PMID: 36733912<\/span><\/span><\/span><\/p>\n

2. Durand AL, Dufour A, Aubert-Foucher E, Oger-Desfeux C, Pasdeloup M, Lustig S, Servien E, Vaz G, Perrier-Groult E, Mallein-Gerin F, Lafont JE (2020). The Lysine Specific Demethylase-1 Negatively Regulates the COL9A1<\/em> Gene in Human Articular Chondrocytes. <\/a><\/span>\u00a0Int J Mol Sci.<\/strong> 2020 Aug 31;21(17):6322. doi: 10.3390\/ijms21176322.<\/span> PMID: 32878268<\/span><\/span>.
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3. Lafont JE, Poujade FA, Pasdeloup M, Neyret P, Mallein-Gerin F.<\/span> (2016). Hypoxia potentiates the BMP-2 driven COL2A1 stimulation in human articular chondrocytes via p38 MAPK<\/a>.\u00a0Osteoarthritis & Cartilage.<\/strong><\/em> 2016 May\u00a0;24(5):856-67.\u00a0doi\u00a0: 10.1016\/j.joca.2015.11.017.<\/span><\/p>\n

4. Thoms BL, Dudek KA, Lafont JE and Murphy CL (2013). <\/span>Hypoxia promotes production and inhibits destruction of human articular cartilage<\/a>. Arthritis and Rheum<\/em><\/strong>. 2013 May 65(5)1302-12.\u00a0doi\u00a0: 10.1002\/art.37867.<\/span><\/p>\n

5. Dudek KA\u00a7, Lafont JE\u00a7, Martinez-Sanchez A, Murphy CL. (2010). <\/span>Type II collagen expression is regulated by tissue-specific miR-675 in human articular chondrocytes.<\/a> The Journal of Biol. Chem<\/em><\/strong>. 285 (32)\u00a0: 24381-7.\u00a0doi\u00a0: 10.1074\/jbc.M110.111328.<\/span>
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6. Murphy CL, BL Thoms, RJ Vaghjiani and JE Lafont (2009). <\/span>HIF-mediated\u00a0articular\u00a0chondrocyte\u00a0function:\u00a0prospects\u00a0for\u00a0cartilage\u00a0repair.\u00a0<\/strong><\/a>Arth. Res. and Ther<\/em><\/strong>. 11(1):213<\/span><\/p>\n

7. Lafont JE, Talma S, Hopfgarten C, Murphy CL (2008). <\/span>Hypoxia\u00a0promotes\u00a0the\u00a0differentiated\u00a0human\u00a0articular\u00a0chondrocyte\u00a0phenotype\u00a0through\u00a0SOX9-dependent\u00a0and -independent\u00a0pathways.<\/a> The Journal of Biol. Chem<\/em><\/strong>. 283 (8) 4778-4786.<\/span><\/p>\n

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Collaborations :<\/strong><\/em><\/span><\/p>\n

Pr. M. Cohen Solal, Bioscar Laboratory (U1132), Hopital Lariboisi\u00e8re, Paris<\/p>\n

Pr. S. Lustig and E. Servien, H\u00f4pital de la Croix-rousse, Lyon<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Project leader : J\u00e9r\u00f4me Lafont Participants\u00a0\u00a0: F. Mallein-Gerin, M. Pasdeloup, S. Moustaghfir Although many epigenetic modifications have been described during osteoarthritis (OA), the precise contribution of the chromatin remodeling enzymes during OA is still unclear. The histone demethylase LSD-1 (Lysine-Specific-Demethylase-1) is up-regulated in OA joints and induces the expression of inflammatory molecules such as mPges-1.<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-1917","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/1917","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1917"}],"version-history":[{"count":38,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/1917\/revisions"}],"predecessor-version":[{"id":5451,"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=\/wp\/v2\/pages\/1917\/revisions\/5451"}],"wp:attachment":[{"href":"https:\/\/lbti.ibcp.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1917"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}