Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4

Differentiation of mouse embryonic stem (ES) cells via embryoid bodies was established as a suitable model to study development in vitro. Here, we sho w that differentiation of ES cells in vitro into chondrocytes can be modula ted by members of the transforming growth factor-beta family (TGF-beta(1), BMP-2 and -4). ES cell differentiation into chondrocytes was characterized by the appearance of Alcian blue-stained areas and the expression of cartil age-associated genes and proteins. Different stages of cartilage differenti ation could be distinguished according to the expression pattern of the tra nscription factor scleraxis, and the cartilage matrix protein collagen II. The number of Alcian-blue-stained areas decreased slightly after applicatio n of TGF-beta(1), whereas BMP-2 or -4 induced chondrogenic differentiation. The inducing effect of BMP-2 was found to be dependent on the time of appl ication, consistent with its sole to recruit precursor cells to the chondro genic fate. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.