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. 2022 Jan 28;12:772237. doi: 10.3389/fphar.2021.772237

TABLE 1.

The role of the Fox subfamilies in osteogenic differentiation.

Fox genes Expression Target genes/pathway Effects on osteogenesis Cells/animal model Reference
FoxO1 Increased Runx2, ALP, OCN Promoted C3H10T1/2 cells Teixeira et al. (2010)
FoxO1 Increased miR-424/FGF2, Runx2 Promoted BMSCs Li et al. (2017)
FoxO1/3/4 Deleted PPARγ, Runx2, Osx, p66shc Inhibited Deletion of FoxO1/3/4 mice Ambrogini et al. (2010)
FoxO1/3/4 Deleted Wnt/β-catenin, cyclin D1 Promoted Bipotential progenitors of osteoblast and adipocytes Iyer et al. (2013)
FoxO3a Increased ALP, OCN, Runx2, LRP5, LRP6 Promoted BMSCs Sun et al. (2018)
FoxO3a Increased OCN, Runx2 Inhibited MC3T3-E1 cells Tang et al. (2019)
FoxC1 Decreased Msx2, Runx2, ALP Inhibited C2C12 cells Hopkins et al. (2016)
Decreased Runx2, osterix Promoted MC3T3 cells Hopkins et al. (2016)
FoxC1 Increased Msx2, Runx2, ALP Promoted C2C12 cells Mirzayans et al. (2012)
FoxC1 KD Msx2, ALP, OCN, Runx2 Promoted O9-1 cells Sun et al. (2013)
FoxC2 Increased ALP, OCN, Cbfα1, Wnt/β-catenin, BSP, PPARγ2 Promoted BMSCs (Lin et al., 2016)
FoxP1 OE Recombination signal-binding protein, ALP Promoted C3H10T1/2 cells Li et al. (2017)
KO ALP, COL1A1, PPARG, CEBPA, FABP4 Inhibited BMSCs Li et al. (2017)
FoxP1/2/4 Decreased Runx2 Promoted Skeletal progenitor cells Zhao et al. (2015)
FoxA2 KD ERK, ALP, OPN, OCN, Runx2, Col1a1 Promoted BMMSCs Ye et al. (2018)
FoxD3 OE OSX, TNAP, SOX9, OPN Promoted hESCs Kamaldinov et al. (2018)
FoxD3 Increased Wnt/β-catenin Inhibited BMMSCs Huang and Chen, (2017)
FoxF1 KD Wnt/β-catenin Promoted BMSCs Shen et al. (2020)
FoxF1 Increased TGF/β-catenin Promoted BMSCs (Weng et al., 2019)
FoxM1 Decreased RANKL/OPG, ALP Promoted PDLCs Li et al. (2019)
FoxQ1 Increased Wnt/β-catenin, ANXA2, ALP, OCN, OPG, Runx2 Promoted BMSCs Xiang et al. (2020)
FoxI1 Deleted Fgf8 Inhibited Foxi1 mutant embryo Nissen et al. (2003)
FoxI3 Deleted Pax8, Fgf3 Inhibited Foxi3 mutant Mice Edlund et al. (2014)
FoxL2 Deleted GH/IGF1, SOX9 Inhibited FoxL2−/− mice Marongiu et al. (2015)
FoxG1 Decreased Osteocalcin, ALP Inhibited Osteoblasts Uchida et al. (2018)

Note. OE, overexpression; KD, knock down; BMSCs, bone marrow mesenchymal stem cells; BMMSCs, bone marrow‐derived mesenchymal stem cells; PDLCs, periodontal ligament cells; hESCs, human embryonic stem cells; ALP, alkaline phosphatase; Runx2, Runt-related transcription factor 2; OCL, osteocalcin; PPARγ, proliferator-activated receptor γ2; msx2, msh homeobox 2; ERK, extracellular-regulated protein kinases; RANKL, receptor activator of nuclear factor-κB ligand.