Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3

Abstract

Runx2 and Sp7 are essential transcription factors for osteoblast differentiation. However, the molecular mechanisms responsible for the proliferation of osteoblast progenitors remain unclear. The early onset of Runx2 expression caused limb defects through the Fgfr1–3 regulation by Runx2. To investigate the physiological role of Runx2 in the regulation of Fgfr1–3, we compared osteoblast progenitors in Sp7−/− and Runx2−/− mice. Osteoblast progenitors accumulated and actively proliferated in calvariae and mandibles of Sp7−/− but not of Runx2−/− mice, and the number of osteoblast progenitors and their proliferation were dependent on the gene dosage of Runx2 in Sp7−/− background. The expression of Fgfr2 and Fgfr3, which were responsible for the proliferation of osteoblast progenitors, was severely reduced in Runx2−/− but not in Sp7−/− calvariae. Runx2 directly regulated Fgfr2 and Fgfr3, increased the proliferation of osteoblast progenitors, and augmented the FGF2-induced proliferation. The proliferation of Sp7−/− osteoblast progenitors was enhanced and strongly augmented by FGF2, and Runx2 knockdown reduced the FGF2-induced proliferation. Fgfr inhibitor AZD4547 abrogated all of the enhanced proliferation. These results indicate that Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation, at least partly, by regulating Fgfr2 and Fgfr3 expression.

Cyclic compression emerged dual effects on the osteogenic and osteoclastic status of LPS-induced inflammatory human periodontal ligament cells according to loading force

“…Therefore, we speculated that appropriate cyclic pressure may promote the osteogenic differentiation in hPDLCs. Combined with the researches that RUNX2 also associated with cell proliferation and could not be used to indicated the role on osteogenic differentiation by itself [28,29]. In the present study, we also detect the expression level of OCN, OPN and OSX, who were regarded as the markers in the maturity of osteoblast and bone mineralization to verify the osteogenic differentiation of hPDLCs after dynamic cyclic stress during LPS-induced inflammation [30,31].…”

Runx2 regulates cranial suture closure by inducing hedgehog, Fgf, Wnt and Pthlh signaling pathway gene expressions in suture mesenchymal cells

“…FGF induces the proliferation of osteoblast lineage cells and increases bone formation in vivo, but inhibits osteoblast differentiation in vitro, while gain-offunction mutations in the FGFR1, FGFR2, and FGFR3 genes cause a number of craniosynostosis syndromes, such as Apert, Crouzon, Pfeiffer, and Muenke syndromes as well as Thanatophoric dysplasia (12,13,32). We also recently reported that Runx2 enhanced the proliferation of osteoblast progenitors through the direct regulation of Fgfr2 and Fgfr3 (33). Canonical Wnt signaling is essential for osteoblast differentiation in both endochondral and intramembranous bones and is required for osteoblast proliferation (14-16, 27, 34).…”

An in vivo Comparison Study Between Strontium Nanoparticles and rhBMP2

“…Interestingly, in our study no significant variation was detected in Runx2 levels. However, our results measured an upregulation of Sp7 (Osterix), indicating OBs differentiation at early and late stage (Santo et al, 2013;Kawane et al, 2018). Sp7 is a transcriptional factor expressed in developing bones regulating the commitment of MSCs toward osteoblastic lineage (Rutkovskiy et al, 2016).…”