Advances in Runx2 regulation and its isoforms.

During the last 10 years, we have witnessed major progress in skeleton biology. Runx2 is an accepted transcription factor essential for osteoblast development from mesenchymal stem cells and maturation into osteocytes and organize crucial events during bone formation. Alternations in Runx2 expression levels are associated with skeletal diseases. In vitro and in vivo studies have reported that multiple integrated complex path ways (such as Wnt/LRP5/beta-catenin, BMP/Smads, 1, 25-(OH)2-vitaminD3/VDR/VDRE pathway, etc.) and several regulatory proteins (such as Msx2, Dlx5, Twists, etc.) play critical roles in modulating Runx2 gene expression, activity, and the subsequent bone formation. These findings provide novel insights through controlling osteoblast differentiation to treat osteoporosis or other bone diseases with altered bone mass by stimulating Runx2 expression. Further studies have shown that expression of RUNX2 is initiated from two promoters, the distal P1 promoter and the proximal P2 promoter. The alternative use of promoters gives rise to the genesis of two major protein isoforms with distinct amino termini, named as Runx2-TypeI and Runx2-TypeII. Here, we also review a complex spatio-temporal pattern of two major isoforms expressions and their possible function differences in skeleton development.