OATAO - Open Archive Toulouse Archive Ouverte Open Access Week

Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis

Nasi, Sonia and So, Alexander and Combes, Christèle and Daudon, Michel and Busso, Nathalie Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis. (2016) Annals of the Rheumatic Diseases, 75 (7). 1372-1379. ISSN 0003-4967

[img]
Preview
(Document in English)

PDF (Author's version) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
361kB

Official URL: http://dx.doi.org/10.1136/annrheumdis-2015-207487

Abstract

Objectives Basic calcium phosphate (BCP) crystal and interleukin 6 (IL-6) have been implicated in osteoarthritis (OA). We hypothesise that these two factors may be linked in a reciprocal amplification loop which leads to OA. Methods Primary murine chondrocytes and human cartilage explants were incubated with hydroxyapatite (HA) crystals, a form of BCP, and the modulation of cytokines and matrix-degrading enzymes assayed. The ability of IL-6 to stimulate chondrocyte calcification was assessed in vitro. The mechanisms underlying the effects of HA on chondrocytes were investigated using chemical inhibitors, and the pathways mediating IL-6-induced calcification characterised by quantifying the expression of genes involved in chondrocyte mineralisation. The role of calcification in vivo was studied in the meniscectomy model of murine OA (MNX), and the link between IL-6 and cartilage degradation investigated by histology. Results In chondrocytes, BCP crystals stimulated IL-6 secretion, further amplified in an autocrine loop, through signalling pathways involving Syk and PI3 kinases, Jak2 and Stat3 molecules. Exogenous IL-6 promoted calciumcontaining crystal formation and upregulation of genes involved in calcification: the pyrophosphate channel Ank, the calcium channel Annexin5 and the sodium/ phosphate cotransporter Pit-1. Treatment of chondrocytes with IL-6 inhibitors significantly inhibited IL-6-induced crystal formation. In meniscectomised mice, increasing deposits of BCP crystals were observed around the joint and correlated with cartilage degradation and IL-6 expression. Finally, BCP crystals induced proteoglycan loss and IL-6 expression in human cartilage explants, which were reduced by an IL-6 inhibitor. Conclusions BCP crystals and IL-6 form a positive feedback loop leading to OA. Targeting calciumcontaining crystal formation and/or IL-6 are promising therapeutic strategies in OA

Item Type:Article
Additional Information:Thanks to BMJ Publishing Group. The original PDF of the article can be found at Thermochimica Acta website : http://dx.doi.org/10.1136/annrheumdis-2015-207487
HAL Id:hal-01647940
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - INPT (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UPS (FRANCE)
Other partners > Centre hospitalier universitaire vaudois - CHUV (SWITZERLAND)
Other partners > Assistance publique - Hôpitaux de Paris - AP-HP (FRANCE)
Other partners > Université de Lausanne - UNIL (SWITZERLAND)
Laboratory name:
Statistics:download
Deposited By: Christele COMBES
Deposited On:24 Nov 2017 15:45

Repository Staff Only: item control page