MicroRNAs (miRNAs) play critical roles in a variety of biological processes in 
diverse organisms, including mammals. In the mouse skeletal system, a global 
reduction of miRNAs in chondrocytes causes a lethal skeletal dysplasia. However, 
little is known about the physiological roles of individual miRNAs in 
chondrocytes. The miRNA-encoding gene, Mir140, is evolutionarily conserved among 
vertebrates and is abundantly and almost exclusively expressed in chondrocytes. 
In this paper, we show that loss of Mir140 in mice causes growth defects of 
endochondral bones, resulting in dwarfism and craniofacial deformities. 
Endochondral bone development is mildly advanced due to accelerated hypertrophic 
differentiation of chondrocytes in Mir140-null mice. Comparison of profiles of 
RNA associated with Argonaute 2 (Ago2) between wild-type and Mir140-null 
chondrocytes identified Dnpep as a Mir140 target. As expected, Dnpep expression 
was increased in Mir140-null chondrocytes. Dnpep overexpression showed a mild 
antagonistic effect on bone morphogenetic protein (BMP) signaling at a position 
downstream of Smad activation. Mir140-null chondrocytes showed lower-than-normal 
basal BMP signaling, which was reversed by Dnpep knockdown. These results 
demonstrate that Mir140 is essential for normal endochondral bone development 
and suggest that the reduced BMP signaling caused by Dnpep upregulation plays a 
causal role in the skeletal defects of Mir140-null mice.