β-Catenin Does Not Co-activate Vitamin D Receptor–mediated Transcription in Osteoblastic and Non-osteoblastic 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 anti-sclerostin 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 vitamin D response element (VDRE) 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.