Activation of EphB4 receptor by Ephrin B2, inhibits the expression of IL‐1β, IL‐6 and RANKL, but not of OPG (Kwan Tat, Pelletier, Amiable, et al., 2008; Kwan Tat, Pelletier, Lajeunesse, et al., 2008), suggesting that activation of EphB4 by ephrin B2 is involved in the altered subchondral bone metabolism in osteoarthritis by reducing resorption factors levels and function. This evidence concerns the gene TNFSF11 and osteoarthritis.