ECTS Abstracts (2015) 1 P230

Osteoclasts Activate Chondrocyte Catabolism through S1P Production

Chahrazad Cherifi, Hang-Korng Ea, Thomas Funck-Brentano, Eric Hay & Martine Cohen-Solal

Inserm U1132 and university Paris 7, Paris, France.

Background: Subchondral bone features accompany all stages of osteoarthritis (OA). We have previously demonstrated that high osteoclastogenesis and bone remodelling is observed at the initiation of OA, while inhibition of osteoclast function prevents bone and cartilage catabolism in murine OA models. Our purpose was to evaluate how osteoclast-derived factors affect the chondrocyte metabolism and to further investigated the role of sphingosine 1 phosphate (S1P), an osteoclast-secreted molecule in chondrocyte metabolism and osteoarthritis.

Methods: Primary murine chondrocytes were cultured with conditioned medium of osteoclasts (Oc-M) or RAW cells (Raw-CM) to analyse the expression of catabolism and anabolism genes (RT-qPCR). Femoral head explants were cultured in the presence of Oc-CM to quantify matrix protein expression and proteoglycan content and further investigate the role of S1P released in Oc-CM in the presence of JTE-013, a S1P receptor 2 (S1PR2) antagonist.

Results: Oc-CM reduced the proteoglycan release in primary chondrocytes and activated MAPkinase pathway. Increased expression of catabolic enzymes (MMP-3, -13, Adamts-4,-5) was observed only with Oc-CM while reduction of expression of anabolic markers (Col2, ACAN, Sox9) was induced by both Oc-CM and Raw-CM. Oc-CM increased the chondrocytic expression of S1P receptors 1 to 4 and the inhibition of S1PR2 protected chondrocytes from degradation enzymes induced by Oc-CM. In joint explants, JTE-013 reversed proteoglycan loss and NITEGE expression induced by Oc-CM, and reduced proteoglycan release and expression of MMP-3 / MMP-13 by the chondrocytes. Our results indicate that S1P produced by osteoclasts promotes chondrocyte catabolism.

Conclusion: These data demonstrate that osteoclast-secreted factors disrupt the balance of chondrocyte metabolism through the production of S1P. Therefore, subchondral bone manipulations may affect chondrocyte function and OA.

Disclosure: The authors declared no competing interests.

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