Dickkopf-related Protein 2 Promotes Hair Growth by Upregulating the Wnt/β-catenin Signaling Pathway in Human Dermal Papilla Cells

The Wnt/β-catenin signaling pathway is crucial for the development, initiation, and growth of hair follicles (HFs). The Dickkopf-related protein (DKK) gene family encodes secreted proteins modulating the Wnt/β-catenin signaling pathway. Studies have reported that DKK1 promotes the regression of HFs and serves as a pathogenic mediator in male pattern baldness. However, the role of DKK2 on human hair growth has not yet been explored. This study investigates direct effect of DKK2 on hair growth using human dermal papilla cell (DPC) cultures and human HF organ cultures. To elucidate the effect of DKK2 on hair growth, we examined the effect of recombinant human DKK2 (rhDKK2) treatment on cell viability, expression of mRNA and protein related to the Wnt/β-catenin signaling pathway, and cell growth in cultured human DPCs. We also performed organ culture of HFs with rhDKK2 and measured changes in hair shaft length for 8 days. Treatment with rhDKK2 led to a dose-dependent rise in the proliferation of human DPCs (