We’re not calling the miRNA 23a,27a,24-2 cluster a bunch of biological bad-guys, but if you’re a progenitor cell hoping to one day become an osteoblast, then they aren’t exactly your best friends. A new study reveals that the miRNA 23a,27a,24-2 cluster is at the center of a regulatory network that controls osteoblast differentiation.
The new network, uncovered by Mohammad Hassan and colleagues at the University of Massachusetts Medical School involves the miR-23a,27a,24-2 cluster, Runx2, an essesntial transcription factor in osteoblastogenesis, and another critical osteoblast regulator, SATB2. The team dissected the regulatory circuit and found out how it controls osteocyte differentiation and bone formation.
- The miR-23a,27a,24-2 cluster targets SATB2, slowing down osteoblastogenesis
- Runx2 keeps the miR-23a,27a,24-2 cluster transcription in check by binding to the cluster’s promoter
- miR-23a,27a,24-2 over-expression experiments show that the cluster inhibits osteoblast differentiation, while knockdown of the miRNAs restored osteoblast development.
- Once osteocytes are terminally differentiated, miR-23a then targets Runx2 to complete the cycle.
So when the miR-23a,27a,24-2 cluster expression is up, osteocyte differentiation comes to a halt, but when Runx2 knocks those miRNAs down, differentiation moves ahead at full speed.
Read all the bone shattering info for yourself at PNAS, November 2010.