Compactin enhances osteogenesis in murine embryonic stem cells

Embryonic stem (ES) cells have the capacity to differentiate into various c ell types in vitro. In this study, we show that retinoic acid is important for the commitment of ES cells into osteoblasts. Culturing retinoic acid tr eated ES cells in the presence of the osteogenic supplements ascorbic acid and P-glycerophosphate resulted in the expression of several osteoblast mar ker genes, osteocalcin, alkaline phosphatase, and osteopontin. However, the re was only a slight amount of mineralized matrix secretion. Addition of bo ne morphogenic protein-a or compactin, a drug of the statin family of HMG-C oA reductase inhibitors, resulted in a greatly enhanced formation of bone n odules. Compactin did not modify the expression of osteogenic markers, but at the late stage of differentiation promoted an increase in BMP-S expressi on. These results establish ES-cell derived osteogenesis as an effective mo del system to study the molecular mechanisms by which the statin compactin promotes osteoblastic differentiation and bone nodule formation. (C) 2001 A cademic Press.