Regulation of osteoblast differentiation by Runx2.

Runx2 protein is first detected in preosteoblasts, and the expression is upregulated in immature osteoblasts, but downregulated in mature osteoblasts. Runx2 is the first transcription factor required for determination of the osteoblast lineage, while Sp7 and canonical Wnt-signaling further direct the fate of mesenchymal cells to osteoblasts, blocking their differentiation into chondrocytes. Runx2 induces the differentiation of multipotent mesenchymal cells into immature osteoblasts, directing the formation of immature bone, but Runx2 inhibits osteoblast maturation and mature bone formation. Normally, the protein level of Runx2 in osteoblasts reduces during bone development, and osteoblasts acquire mature phenotypes, which are required for mature bone formation. Furthermore, Runx2 triggers the expression of major bone matrix genes during the early stages of osteoblast differentiation, but Runx2 is not essential for the maintenance of these gene expressions in mature osteoblasts.