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RUNX2 regulates <jats:italic>Sp7<\/jats:italic> expression at an early stage of osteoblast differentiation. FGF2 upregulates <jats:italic>Runx2<\/jats:italic> expression and activates RUNX2, and gain\u2010of\u2010function mutations of FGFRs cause craniosynostosis and limb defect with upregulation of <jats:italic>Runx2<\/jats:italic> expression. Wnt signaling upregulates <jats:italic>Runx2<\/jats:italic> expression and activates RUNX2, and RUNX2 induces <jats:italic>Tcf7<\/jats:italic> expression. IHH is required for <jats:italic>Runx2<\/jats:italic> expression in osteoprogenitor cells during endochondral bone development, and RUNX2 directly regulates <jats:italic>Ihh<\/jats:italic> expression in chondrocytes. Thus, RUNX2 regulates osteoblast differentiation and chondrocyte maturation through the network with SP7 and with FGF, Wnt, and IHH signaling pathways during skeletal development. J. Cell. 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