Abstract
Runx2 is essential for osteoblast differentiation and chondrocyte maturation. During osteoblast differentiation, Runx2 is weakly expressed in uncommitted mesenchymal cells, and its expression is upregulated in preosteoblasts, reaches the maximal level in immature osteoblasts, and is down-regulated in mature osteoblasts. Runx2 enhances the proliferation of osteoblast progenitors by directly regulating Fgfr2 and Fgfr3. Runx2 enhances the proliferation of suture mesenchymal cells and induces their commitment into osteoblast lineage cells through the direct regulation of hedgehog (Ihh, Gli1, and Ptch1), Fgf (Fgfr2 and Fgfr3), Wnt (Tcf7, Wnt10b, and Wnt1), and Pthlh (Pthr1) signaling pathway genes, and Dlx5. Runx2 heterozygous mutation causes open fontanelle and sutures because more than half of the Runx2 gene dosage is required for the induction of these genes in suture mesenchymal cells. Runx2 regulates the proliferation of osteoblast progenitors and their differentiation into osteoblasts via reciprocal regulation with hedgehog, Fgf, Wnt, and Pthlh signaling molecules, and transcription factors, including Dlx5 and Sp7. Runx2 induces the expression of major bone matrix protein genes, including Col1a1, Spp1, Ibsp, Bglap2, and Fn1, in vitro. However, the functions of Runx2 in differentiated osteoblasts in the expression of these genes in vivo require further investigation.
Highlights
Runx2 belongs to the Runx family, which has the DNA-binding domain runt, and consists of Runx1, Runx2, and Runx3 [1]
Runx2 is expressed in uncommitted mesenchymal cells, and its expression is upregulated in preosteoblasts, reaches the maximum level in immature osteoblasts, and is down-regulated in mature osteoblasts [13,14]
Runx2, Fgfr2, and Fgfr3 are expressed in the mesenchymal cells in Sp7–/– mice at levels comparable to those in osteoblasts in wild-type mice. These suggest that mesenchymal cells in Sp7–/– mice are preosteoblasts and that Sp7–/– mice are an appropriate model for the investigation of preosteoblast proliferation because osteoblast differentiation is blocked at the preosteoblast stage
Summary
Runx belongs to the Runx family, which has the DNA-binding domain runt, and consists of Runx, Runx, and Runx3 [1]. Runx2-deficient (Runx2–/–) mice lack osteoblasts and bone formation, and chondrocyte maturation is markedly inhibited [7,9,10,11]. Runx directly regulates Sp7 expression, and osteoblasts and bone formation are absent in Sp7–/R– umnixc2ed[i2r3e,c2tl4y].reAgsulRautensxS2p7iseaxnpruespssiotrne,aamndtroasntesocbrilpasttisonanfdacbtoonreoffoSrmp7a,tiRonunaxre2ailssoexapbrseesnsteidn in. In conditional Ctnnb knockout mice created by crossing with Twist (Dermo1) Cre knock-in mice in which Ctnnb is deleted in osteo-chondroprogenitors, osteoblasts are absent, Runx is expressed in the perichondrial cells, and Sp7 expression is weak or absent in perichondrial cells [27,28]. As some of the mesenchymal cells in the perichondrium and calvaria differentiate into chondrocytes in Sp7–/– mice and conditional Ctnnb1–/– mice, Sp7 and canonical Wnt signaling inhibit chondrocyte differentiation and direct Runx2+ osteoblast progenitors to become osteoblasts (Figure 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
