BMP‐2 Regulates the Formation of Oral Sulcus in Mouse Tongue by Altering the Balance Between TIMP‐1 and MMP‐13

The aim of this study is to investigate whether BMP‐2 regulates the oral sulcus formation of mouse embryonic tongue by modifying the expression of TIMP and MMP. The BMP‐2 siRNA induced a 180% increase in the depth of oral sulcus cavity (P < 0.01) by stimulating the invagination of oral sulcus into the mesenchymal tissues consisting of tongue floor, whereas the recombinant BMP‐2 suppressed the process in the organ culture system of mouse embryonic tongue. The BMP‐2 siRNA induced a 60% decrease in the expression of TIMP‐1 mRNA (P < 0.05) and a drastic decline in TIMP‐1 protein was observed around the oral sulcus in the BMP‐2 siRNA treated mandibles. The recombinant BMP‐2 induced a 220% increases in the expression of TIMP‐1 mRNA and the area of the immunostaining for TIMP‐1 around the oral sulcus was larger in the mandibles treated with the recombinant BMP‐2 than the vehicle. The BMP‐2 siRNA induced a 60% increase in the expression of MMP‐13 protein and a marked increase in the staining intensity for MMP‐13 was observed in the epithelial region of the BMP‐2 siRNA treated mandibles. The recombinant BMP‐2 induced a 70% decrease in the expression of MMP‐13 mRNA and the decrease was mainly observed in the tissues around oral sulcus. The expressions of BMP‐2, TIMP‐1, and MMP‐13 were verified in the tissues around in vivo developing oral sulcus at E11, 12, and 13 by immunohistochemistry. These results suggest that BMP‐2 regulates the formation of oral sulcus by altering the balance between TIMP‐1 and MMP‐13. Anat Rec 293:1408–1415, 2010. © 2010 Wiley‐Liss, Inc.