In hair follicle cells APCDD1 inhibits the canonical WNT/beta-Catenin pathway and its inactivation is associated with an autosomal dominant form of hair loss. We analyzed the role of APCDD1 for the osteogenic differentiation in dental follicle cells (DFCs) and identified a new and surprising function. Contrarily to hair follicle cells APCDD1 was crucial for the expression of beta-Catenin and for the activity of the TCF/LEF reporter assay in DFCs. In addition, a depletion of APCDD1 inhibits the expression of osteogenic markers such as RUNX2 and decreased the matrix mineralization. However, similar to hair follicle cells in previous studies a control cell culture with oral squamous carcinoma cells showed that APCDD1 inhibits the expression of beta-Catenin and of typical target genes of the canonical WNT/beta-Catenin pathway. In conclusion, our data disclosed an unusual role of APCDD1 in DFCs during the osteogenic differentiation. APCDD1 sustains the expression and activation of beta-Catenin. (C) 2015 Elsevier Inc. All rights reserved.