DKK-1, Human

Dickkopf related protein 1 (DKK-1) is a chemokine that belongs to the DKK protein family, which also includes DKK-2, DKK-3 and DKK-4. DKK-1 was originally identified as a Xenopus head forming molecule that behaves as an antagonist for Wnt signaling. It is one of the most up-regulated genes during androgen-potentiated balding, with DKK-1 messenger RNA up-regulated a few hours after DHT treatment of hair follicles at the dermal papilla in vitro. Neutralizing bodies against DKK-1 reverses DHT effects on outer root sheath keratinocytes. DKK-1 expression is attenuated by L-threonate, a metabolite of ascorbate in vitro. DKK-1 promotes LRP6 internalization and degradation as it forms a ternary complex with the cell surface receptor Kremen. DKK-1 not only functions as a head inducer during development, but also regulates joint remodeling and bone formation, which indicate sits role in the pathogenesis of rheumatoid arthritis and multiple myeloma.