Wnt/β-catenin signaling in bone marrow niche

Abstract

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.

Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway

“…Wnt/β-catenin signaling is an essential pathway in the osteogenic differentiation of MSCs1415. Wnt signaling results in cellular accumulation of Wnt/β-catenin, followed by nuclear translocation of β-catenin and activation of target genes31.…”

“…Wnt/β-catenin signaling is a crucial regulator of MSCs13 and plays an essential role in osteogenic differentiation1415. Disruption of β-catenin leads to extensive bone marrow adiposity and low bone mass16.…”

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

“…As we know, osteoblasts are derived from mesenchymal stem cells (MSCs). Wnt canonical signaling plays an important role in osteoblast differentiation both during embryogenesis and in adult life (50). However, there are several novel members in the LDLR family such as, LRP3, LRP10 and LRP12 (25,29,40), which are uncertain if they are receptors for apoE.…”

Pathophysiology and therapeutic options in osteogenesis imperfecta: an update

“…Components of the canonical Wnt/β-catenin signaling pathway are integral for normal osteoblast differentiation as well as the differentiation of several types of stem cells. 32 Fahiminiya et al 33 have reported WNT1 mutations in four children from three families. These children had short stature, low bone density, and multiple vertebral compression fractures in addition to multiple long-bone fractures during the first years of life.…”