Matrix metalloproteinase-3 mediates cardiac differentiation of mouse embryonic stem cells

Recently, it was shown that the Bmp antagonist Noggin could strongly induce cardiomyocyte differentiation by transient treatment of undifferentiated ES cells. In order to determine how Noggin may induce cardiac differentiation, we compared differentially expressed genes during Noggin treatment of ES cells using microarray analysis and found that matrix metalloproteinase (Mmp)-3 is the only gene whose expression is increased by Noggin treatment. Keywords: embryonic stem cells, cardiac differentiation, matrix metalloproteinase-3, Noggin To induce differentiation, 150ng/ml of Noggin (Sigma, St. Louis, MO) was added to the culture medium for 3 days. Then the cells were trypsinized and cultured in culture medium without Lif on uncoated Petri dishes to induce EB formation. On the second day after EB formation, Noggin was removed from the culture medium. For the Noggin treated group, total RNA from undifferentiated ES cells, cells treated with Noggin for 3 days, and EBs either 2 or 4 days after EB formation were isolated using Trizol reagent (Invitrogen, Calsbard, CA). For the non-treated control group, undifferentiated ES cells and EBs either 2 or 4 days after EB formation were isolated.