Ahmadzadeh Ahmad, Norozi Fatemeh, Shahrabi Saeid, Shahjahani Mohammad, Saki Najmaldin
Health Research Institute, Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Cell Tissue Res. 2016 Feb;363(2):321-35. doi: 10.1007/s00441-015-2300-y. Epub 2015 Oct 16.
The bone marrow (BM) niche is a specific physiological environment for hematopoietic and non-hematopoietic stem cells (HSCs). Several signaling pathways (including Wnt/β-catenin) regulate various aspects of stem cell growth, function and death in the BM niche. In addition, the canonical Wnt pathway is crucial for directing self-renewal and differentiation as important mechanisms in many types of stem cells. We review the role of the Wnt/β-catenin pathway in the BM niche and its importance in stem cells. Relevant literature was identified by a PubMed search (1997-2014) of English-language literature by using the following keywords: BM niche, Wnt/β-catenin signaling, osteoblast, osteoclast and bone disease. The Wnt/β-catenin pathway regulates the stability of the β-catenin proto-oncogene. The stabilized β-catenin then translocates to the nucleus, forming a β-catenin-TCF/LEF complex regulating the transcription of specific target genes. Stem cells require β-catenin to mediate their response to Wnt signaling for maintenance and transition from the pluripotent state during embryogenesis. In adult stem cells, Wnt signaling functions at various hierarchical levels to contribute to the specification of the diverse tissues. Aberrant Wnt/β-catenin signaling and its downstream transcriptional regulators are observed in several malignant stem cells and human cancers. Because Wnt signaling can maintain stem cells and cancer cells, the ability to modulate the Wnt pathway either positively or negatively may be of therapeutic relevance. The controlled activation of Wnt signaling might allow us to enhance stem and progenitor cell activity when regeneration is needed.
骨髓（BM）生态位是造血干细胞和非造血干细胞（HSCs）的特定生理环境。几种信号通路（包括Wnt/β-连环蛋白）调节骨髓生态位中干细胞生长、功能和死亡的各个方面。此外，经典Wnt通路对于指导自我更新和分化至关重要，是许多类型干细胞的重要机制。我们综述了Wnt/β-连环蛋白通路在骨髓生态位中的作用及其在干细胞中的重要性。通过使用以下关键词对1997年至2014年的英文文献进行PubMed检索来确定相关文献：骨髓生态位、Wnt/β-连环蛋白信号传导、成骨细胞、破骨细胞和骨疾病。Wnt/β-连环蛋白通路调节β-连环蛋白原癌基因的稳定性。稳定的β-连环蛋白随后转运至细胞核，形成β-连环蛋白-TCF/LEF复合物，调节特定靶基因的转录。干细胞需要β-连环蛋白来介导其对Wnt信号的反应，以维持并在胚胎发育过程中从多能状态转变。在成体干细胞中，Wnt信号在不同层次水平发挥作用，有助于不同组织的特化。在几种恶性干细胞和人类癌症中观察到异常的Wnt/β-连环蛋白信号传导及其下游转录调节因子。由于Wnt信号可以维持干细胞和癌细胞，正向或负向调节Wnt通路的能力可能具有治疗意义。在需要再生时，对Wnt信号的可控激活可能使我们能够增强干细胞和祖细胞的活性。
