β-catenin does not co-activate vitamin D receptor-mediated transcription in osteoblastic and nonosteoblastic cells.

Vitamin D (VD) and Wnt signaling both play important roles in bone metabolism and are targeted in osteoporosis therapy. Combination treatment with VD derivatives and antisclerostin antibodies that activate Wnt signaling improves clinical outcomes, although the molecular basis of this cooperative effect remains unclear. Because β-catenin functions as a transcriptional co-regulator in canonical Wnt signaling, we examined whether β-catenin modulates vitamin D receptor (VDR)-mediated transcription. Reporter assays were performed in Saos-2 osteoblastic cells using VD response element and TCF/LEF-responsive reporters. Activation of Wnt signaling by CHIR99021 or expression of constitutively active β-catenin did not enhance VDR transcriptional activity but modestly suppressed VD-induced transcription. Similar results were obtained in HCT116 and COS-1 cells. These findings indicate that VDR and Wnt/β-catenin signalings are not cross-talked at the transcriptional level.