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.
Find out more about the Lenti-miR™ miRNA precursors and miRZip™ miRNA inhibition constructs used in this paper at the System Bioscience website.