Parathyroid hormone (PTH) suppresses Dickkopf 1 (Dkk1) expression in 
osteoblasts. To determine whether this suppression is essential for PTH-mediated 
Wnt signaling and bone formation, we examined mice that overexpress Dkk1 in 
osteoblasts (Dkk1 mice). Dkk1 mice were osteopenic due to abnormal osteoblast 
and osteoclast activity. When fed a low-calcium diet, and in two other models of 
hyperparathyroidism, these mice failed to develop the peritrabecular stromal 
cell response ("osteitis fibrosis") and new bone formation seen in wild-type 
mice. Despite these effects of Dkk1 overexpression, PTH still activated Wnt 
signaling in Dkk1 mice and in osteoblastic cells cultured from these mice. In 
cultured MC3T3E1 preosteoblastic cells, PTH dramatically suppressed Dkk1 
expression, induced PKA-mediated phosphorylation of beta-catenin, and 
significantly enhanced Lef1 expression. Our findings indicate that the full 
actions of PTH require intact Wnt signaling but that PTH can activate the Wnt 
pathway despite overexpression of Dkk1.