Recently, large body of evidences that Wnt plays an important role in regulation of tissue patterning and skeletogenesis including membranous and enchondral ossification is accumulating. Several genetic studies also indicate that low density lipoprotein receptor related protein (LRP) 5, LRP6, beta-catenin and lymphoid enhancer-binding factor/T-cell factor (LEF/TCF) participate in osteogenic action induced by Wnt family members. In contrast, secreted Frizzled-related proteins and dickkopf (Dkk) proteins, natural Wnt inhibitory factors, inhibit Wnt-dependent osteogenesis, presumably functioning as a negative feedback loop. In addition, Wnt signaling interacts with BMP signaling, thereby modulating its osteogenic action. Thus, the network systems of Wnt signaling temporally and spatially controls osteogenic action of Wnt family members.