Rosiglitazone has the potential to activate peroxisome proliferator-activated receptor-? (PPAR?), which in turn can affect bone formation and resorption. However, the mecha-nisms by which rosiglitazone regulates osteoclastic or osteoblastic differentiation are not fully understood. This study examines how rosiglitazone affects osteoclast for-mation, bone resorption and osteoblast differentiation from mouse bone marrow. Rosiglitazone treatment not only inhibited the formation of tartrate-resistant acid phosphatase-positive cells, but also prevented pit forma-tion by bone marrow cells in a dose- and time-dependent manner. Rosiglitazone also suppressed the receptor acti-vator of nuclear factor (NF)-?B ligand (RANKL) receptor (RANK) expression but increased PPAR?2 expression in the cells. In addition, rosiglitazone diminished RANKL-induced activation of NF-?B-DNA binding by blocking I?B? phosphorylation. Furthermore, it reduced collagen and osteocalcin levels to nearly zero and prevented mRNA expression of osteoblast-specific proteins including runt-related tran-scription factor-2, osteocalcin, and type I colla-gen. How-ever, mRNA levels of adipocyte-specific marker, aP2, were markedly increased in the cells co-incubated with rosigli-tazone. These results suggest that PPAR? acti-vation by rosiglitazone inhibits osteoblast differentiation with in-creased adipogenesis in bone marrow cells and also may prevent osteoclast formation and bone resorp-tion in the cells.

Keywords: mouse bone marrow cells, osteoblastogenesis, osteoclastogenesis, PPAR?, rosiglitazone