Identification of signaling pathways triggered by BMP-2 and TGF-beta1

Project leader  : E. Aubert-Foucher

Participant  : E. Perrier-Groult

Bone morphogenetic protein (BMP-2) and transforming growth factor (TGF-β1) are multifunctional cytokines both proposed as stimulants for cartilage repair. In this context, we have undertaken to closely examine and compare their effects on the expression of key factors of the chondrocyte phenotype. In fact, we have found that BMP-2 and TGF-β1 exert differential effects on a variety of chondrocytic markers (integrin receptors, type II collagen isoforms). We have identified signaling molecules characteristic of TGF-β/BMP signaling pathways that are involved in these effects. Now, we are looking for the molecular mechanisms by which BMP-2 and TGF-β1 control actin organization (RhoA signaling, actin polymerization…). We have noticed that BMP-2 induces cortical actin whereas TGF-β1 induces stress fibers in the chondrocytes (figure 1) and it is known that actin cytoskeleton and its organization regulate intracellular signaling

Figure 1 : Organization of the actin cytoskeleton in murine chondrocytes cultured in monolayer. BMP-2 induces cortical actin architecture whereas TGF-β1 induces the formation of stress fibers in the cells (fluorescence labeling using rhodamine-conjugated phalloidin).

Selected publications

1. E. Aubert-Foucher, N. Mayer, M. Pasdeloup, A. Pagnon, D. Hartmann, Mallein-Gerin F (2014). A unique tool to selectively detect the chondrogenic IIB form of human type II procollagen protein. Matrix biology, 2014 Feb;34:80-8. PMID: 24055103. doi: 10.1016/j.matbio.2013.09.001.

2. Gouttenoire J, Bougault C, Aubert-Foucher E, Perrier E, Ronzière MC, Sandell L, Lundgren-Akerlund E, Mallein-Gerin F. (2010). BMP-2 and TGF-beta1 differentially control expression of type II procollagen and alpha 10 and alpha 11 integrins in mouse chondrocytes. Eur. J. Cell Biol. 2010 Apr;89(4):307-14. PMID: 20129696. doi: 10.1016/j.ejcb.2009.10.018.