When considered together, studies of the nSMase2 KO mouse and the fro/fro mouse present clear evidence that nSMase2 plays an important role regulating bone development and formation. This was further supported by a recent study reporting regulation of nSMase2 transcription by bone morphogenetic protein-2 (BMP-2) during osteoblasts maturation (Chae et al., 2009). However, it is important to note that the phenotypes between the fro/fro mouse and nSMase2 KO mouse are somewhat different. Unlike in the fro/fro mouse, no abnormal bone mineralization was observed in the nSMase2 KO mice; indeed, bone in the adult nSMase2 KO mice is even stronger than in the wild-type mouse (Stoffel et al., 2007). The underlying mechanisms of this discrepancy are unclear, and may be age related. This requires further investigation.
