Integrin signaling pathways in mesenchymal stem cells

Abstract

This review provides an overview of the integrin signaling pathways and their roles in mesenchymal stem cell differentiation into adipocytes, chondrocytes, and osteoblasts. In these three differentiated cells, the cell extracellular matrix plays an important role in regulating the integrin signaling pathway, as the presence of growth factors and other molecules in the extracellular matrix will affect the cell differentiation. The focus of this review is to elucidate the role of the integrin signaling pathway in adipogenesis, chondrogenesis, and osteogenesis, highlighting its diverse contributions to tissue homeostasis and repair. By synthesizing current knowledge, this paper aims to inspire further research into the therapeutic potential of targeting integrin pathways in stem cell-based tissue engineering.

Keywords: Cell differentiation; Cell signalling; Cell-ECM interactions; Extracellular matrix (ECM); Integrin signalling pathway; Mesenchymal stem cells (MSCs).

Fig. 1

Integrin signaling in MSC-derived lineage differentiation. The activation of integrin regulates a distinct downstream signaling pathway and influences the activity of MSC-derived lineages. In adipocytes, the activation of integrin signaling suppresses FAK production and regulates the Wnt-/β-catenin pathway, and as a result, the adipogenic markers (AP2, AdipoQ, and CEBPα) are downregulated. In chondrocytes, the interaction of TGF-β1 and integrin leads to the activation of Src, and triggers the MAPK-ERK pathways. This activation promotes inflammatory responses, besides regulating cell proliferation and differentiation. In osteoblasts, integrin activation triggers both the Wnt-/β-catenin and FAK/ERK pathways, which subsequently promote bone mineralization and osteogenic differentiation, respectively. Created with BioRender.com