Tipping the balance: modulating the Wnt pathway for tissue repair

Abstract

The Wnt signaling pathway has a crucial role in regulating cell growth and differentiation and is required for tissue homeostasis and repair. Although constitutive activation of the Wnt pathway can lead to abnormal cell growth and cancer, modulation of Wnt signaling might have a therapeutic benefit for tissue regeneration in numerous diseases. Recently, preclinical studies have demonstrated that treatments with antibodies against the Wnt inhibitor Dickkopf1 (DKK1) and with the positive Wnt modulator R-Spondin1 (RSpo1) were sufficient to repair the bone lesions in multiple myeloma and rheumatoid arthritis and to restore the damaged mucosa in experimental colitis, respectively. A remarkable balance is set for Wnt signaling by secreted proteins such as RSpo1 and DKK1, which help to regulate tissue homeostasis. As physiological Wnt response is essential for the regeneration of damaged tissues, modulation of the Wnt pathway might be beneficial for the treatment of multiple human diseases.