Fibronectin and stem cell differentiation - lessons from chondrogenesis

Abstract

The extracellular matrix (ECM) is an intricate network of proteins that surrounds cells and has a central role in establishing an environment that is conducive to tissue-specific cell functions. In the case of stem cells, this environment is the stem cell niche, where ECM signals participate in cell fate decisions. In this Commentary, we describe how changes in ECM composition and mechanical properties can affect cell shape and stem cell differentiation. Using chondrogenic differentiation as a model, we examine the changes in the ECM that occur before and during mesenchymal stem cell differentiation. In particular, we focus on the main ECM protein fibronectin, its temporal expression pattern during chondrogenic differentiation, its potential effects on functions of differentiating chondrocytes, and how its interactions with other ECM components might affect cartilage development. Finally, we discuss data that support the possibility that the fibronectin matrix has an instructive role in directing cells through the condensation, proliferation and/or differentiation stages of cartilage formation.

Fig. 1.

The stages of chondrogenesis. (A) The diagram illustrates the principal steps of chondrogenesis and indicates some of the main ECM proteins that are expressed at different stages throughout the process. The ECM proteins fibronectin (green), collagen I (blue), collagen II and IX (orange) and aggrecan (violet) are shown. (B) Mesenchymal stem cells were induced to undergo chondrogenesis in pellet culture for 12 days in chondrogenic medium containing TGF-β3. At day 12, pellets were harvested, embedded and cut into 5 µm-thick sections, which were fixed and stained. Anti-human fibronectin (HFN7.1) monoclonal antibody staining was followed by Alexa-Fluor-488-conjugated goat anti-mouse immunoglobulin G. The image shows that the fibronectin matrix is present throughout the section (green). Cell nuclei were visualized with 4′,6-diamidino-2-phenylindole (DAPI) and the inset shows the cell density within the section. Scale bar: 100 µm.

Fig. 2.

Potential roles for fibronectin in facilitating progression through the chondrogenesis stages. The principal chondrogenesis steps are illustrated, with fibronectin (green) and collagen matrices (orange) highlighted. Specific cell activities that might involve fibronectin are indicated in red at each step. Please refer to the text for further details.