Figure 3. Wnt signaling determines the cell fate of mesenchymal progenitor cells and regulates bone formation and resorption. The Wnt canonical pathway represses adipocyte differentiation and chondrocyte differentiation from progenitor cells, whereas it is required for the transition of chondrocytes to hypertrophy. In contrast, Wnt pathway activation promotes the osteoblast cell lineage by controlling proliferation, maturation, terminal differentiation, and bone formation. Differentiated osteoblasts and/or osteocytes produce Wnt inhibitors such as Dickkopf (Dkk1) and sclerostin (Sost) proteins as a negative feedback control of osteoblast differentiation and function. Wnt signaling also induces osteoblasts to produce more osteoprotegerin (OPG), increasing the ratio of OPG to receptor activator of NF-κB ligand (RANKL) to decrease osteoclast differentiation and bone resorption.