The Wnt signaling pathway plays essential roles in tissue or organ homeostasis by regulating cell proliferation and differentiation. Upon tissue or organ injury, inflammation is coupled with tissue repair and regeneration process. The canonical Wnt signaling transduction pathway is crucial for cell proliferation, cell differentiation, and tissue regeneration. Dickkopf1 (DKK1) is a quintessential Wnt antagonist that inhibits the Wnt-mediated tissue repair process. Recent studies reported increased levels of DKK1 in many diseases such as cancer, infection, and musculoskeletal diseases. In many cases, the role of DKK1 has been identified as a pro-inflammatory ligand and the expression levels are associated with poor disease outcomes. A variety of cell types including platelets, endothelial cells, and cancer cells secrete DKK1 upon stimuli. This puts DKK1 in a unique place to view immune responses from multicellular interactions in tissue injury and repair process. In this review, we discuss recent efforts to address the underlying mechanism regarding the pro-inflammatory role of DKK1 in cancer, bone diseases, and other inflammatory diseases.

Wnt信号通路通过调节细胞增殖和分化，在组织或器官稳态中发挥重要作用。一旦组织或器官受伤，炎症就会伴随组织修复和再生过程。经典的Wnt信号转导途径对于细胞增殖，细胞分化和组织再生至关重要。Dickkopf1（DKK1）是一种典型的Wnt拮抗剂，可抑制Wnt介导的组织修复过程。最近的研究报道，许多疾病（例如癌症，感染和肌肉骨骼疾病）中DKK1的含量增加。在许多情况下，DKK1的作用已被确认为促炎性配体，并且其表达水平与不良的疾病预后相关。刺激后，包括血小板，内皮细胞和癌细胞在内的多种细胞类型分泌DKK1。这使DKK1处于独特的位置，可以查看组织损伤和修复过程中多细胞相互作用产生的免疫反应。在这篇综述中，我们讨论了最近的努力，以解决有关DKK1在癌症，骨骼疾病和其他炎症性疾病中促炎作用的潜在机制。