THU0036 PPAR gamma agonist rosiglitazone could inhibit RA-FLS induced osteoclastogenesis by down-regulating RANKL expression and suppression of ERK phosphorylation

Background Experiments and clinical trial have shown that peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist could inhibit inflammation in rheumatoid arthritis (RA)[1,2]. Recent reports also showed that PPAR-γ agonist could prevent inflammatory periodontal bone loss by inhibiting receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis[3]. However, whether PPAR-γ agonist can inhibit bone erosion by RANKL-mediated osteoclastogenesis in RA is not clearly understood. Objectives To investigate the effects and underlying mechanism of rosiglitazone (RSG), a high-affinity synthetic agonist for PPAR-γ, on rheumatoid synovial fibroblasts (RA-FLS) induced osteoclastogenesis. Methods RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor (M-CSF) and rosiglitazone (0, 15μM) for 14d. Osteoclast formation was assayed by tartrate-resistant acid phosphatase (TRAP) staining, and the RANKL/OPG mRNA was detected by Real-time PCR, the protein expression of RANKL, OPG, p-ERK, p-p38 and p-JNK was measured by Western blot. RA-FLS were cocultured with normal monocytes on bone slices for 14d, and rosiglitazone (0, 15μM) was then added from day 15, resorption lacunae area was identified by toluidine blue staining at day 21 and quantitated by Image Analysis Software. Results 15μM rosiglitazone could significantly decrease the number of osteoclasts [(38±6) vs (85±10) per well,P