Figure 1. A) Villanueva Goldner staining of undecalcified tibia sections of mice at age 9 months. Scale bar, 0.4 mm; C, cortical bone; T, trabecular bone. B) Bone mineral density (BMD) measurements in 20 proximal-to-distal femoral divisions from mice at ages 1, 4, 9 and 14 months (M); WT, wild-type; *P < .05; ** P = .01. C) Regulation of MEKK2 degradation by SMURF1 in the context of bone morphogenetic protein (BMP) signaling and the osteogenic response. By augmenting MEKK2-JNK-JUN/ATF activity, the transcription of many genes involved in the osteogenic response (e.g., the gene for osteocalcin) can be sensitized to the BMP/SMADs, thereby providing an explanation for the phenotype observed in the SMURF1-deficient mice.