Thiazolidinediones inhibit osteoclast-like cell formation and bone resorption in vitro

Osteoblasts and adipocytes are derived from common bone marrow stromal cell s that play crucial roles in the generation of osteoclasts. Activation of p eroxisome proliferator-activated receptor-gamma (PPAR gamma) induces adipog enic differentiation of stromal cells; however, whether this would affect o steoblast/osteoclast differentiation is unknown. Thus, we examined the effe cts of the thiazolidinedione (TZD) class of antidiabetic agents that activa te PPAR gamma on osteoblast/osteoclast differentiation using mouse whole bo ne marrow cell culture. As reported, all TZDs we tested (troglitazone, piog litazone, and BRL 49653) markedly increased the number of Oil Red O-positiv e adipocytes and the expression of adipsin and PPAR gamma 2. 1 alpha,25-Dih ydroxyvitamin D-3 [1,25-(OH)(2)D-3] did not affect adipogenic differentiati on induced by TZDs. TZDs did not affect alkaline phosphatase activity, an e arly marker of osteoblastic differentiation, despite their marked adipogeni c effects. TZDs decreased the number of tartrate-resistant acid phosphatase -positive multinucleated osteoclast-like cells induced by 1,25-(OH)(2)D-3 o r PTH. Troglitazone dose dependently inhibited basal and 1,25-(OH)(2)D-3- a nd PTH-induced bone resorption as assessed by pit formation assay. Interleu kin-11 blocked the induction by troglitazone of adipogenesis, but had no ef fect on the inhibition of osteoclast-like cell formation. These results ind icate that TZDs are potent inhibitors of bone resorption in vitro. Inhibito ry effects of TZDs on osteoclastic bone resorption was not osteotropic fact or specific and did not appear to be related to their adipogenic effects, T hus, TZDs may suppress bone resorption in diabetic patients and prevent bon e loss.