Fig. 6.

Runx2-targeting miRNAs modulate osteogenesis and chondrogenesis. (A) miRNA regulation of Runx2 supports osteogenesis (gray) and chondrogenesis (black). Up-regulation of miRNA expression (upward line) during late stages of osteoblast differentiation may be responsible for the inhibition of Runx2 (narrowing polygon) that permits final stages of maturation. Conversely, decreased miRNA expression (downward line) may contribute to the up-regulation of Runx2 during chondrogenesis (widening triangle). (B) miRNAs that are selectively expressed in osteoblasts (osteo-miRNAs) regulate osteogenesis and chondrogenesis by directly targeting Runx2, a master gene during key stages in these two distinct biological processes. Runx2 is stimulatory for osteogenic lineage commitment (arrow) but inhibitory (blunted arrow) at late stages of osteoblast maturation. Attenuation of Runx2 by miRNAs inhibits bone marker gene expression (i.e., osteopontin and osteocalcin) during osteoblast differentiation.