Wertz S(1), Franchimont N(1), Malaise M(1), Gangji V(2), Van Cauwenberge H(3) and Hauzeur J.Ph(1).

Departments of Rheumatology(1) and Orthopaedic Surgery(3), University of Liège, CHU Sart-Tilman, 4000 Liège; Department of Rheumatology and Rehabilitation(2), Erasme Hospital, University of Brussels, 1070 Brussels, Belgium.

Abnormalities of the mesenchymal stem cells and osteoblastic cells (Obs) might play a role in producing bone collapse due to insufficient repair of the necrotic area in osteonecrosis of the femoral head (ON). Osteoblast and osteocyte apoptosis should be increased at the osteonecrotic site. We compared the TRAIL (TNF-related apoptosis-inducing ligand) cytotoxicity on primary Obs isolated from femoral heads from patients with ON or osteoarthritis (OA) and on two human osteosarcoma cell lines, MG-63 and SaOS2. We showed that ON but also OA Obs were sensitive to TRAIL. We also observed TRAIL cytotoxicity on MG-63 but not SaOS2 cells. Moreover, we saw that TRAIL negatively regulated Akt and ERK survival pathways in MG-63 cells. We also investigated the IL-6 influences on apoptotic response of Obs to TRAIL. Even though decreased IL-6 and sIL-6R levels were observed at peripheral sites of the ON in regard of the levels produced in the iliac crest, IL-6 had no protective effects on TRAIL-induced apoptosis in ON Obs and only a weak protective effect in MG-63 cells. But TRAIL stimulated IL-6 production in MG-63 cells and, to a lesser extend, in SaOS2 cells and OA Obs, suggesting other roles of TRAIL in the bone environment.