Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiation

Table 1 Molecules regulating osteogenesis via the Wnt/β-catenin signaling pathway

No	Name	Experimental model(s)	Effect	Role	Ref.
1	CRYAB	In vitro and in vivo	Promotes osteogenic activity	Acts as a regulator of the osteogenic differentiation of BMSCs and protects β-catenin from proteasomal degradation	[37]
2	LGR6	In vitro and in vivo	Promotes osteogenic activity	LGR6 improves the signaling pathway mediated by Wnt/β-catenin during osteogenesis by stabilizing β-catenin within the cytoplasm	[38]
3	KLF14	In vitro and in vivo	Inhibits osteogenic activity	KLF14 and Wnt3A promoter interaction suppresses the expression of Wnt3A and downstream targets of Wnt signaling during osteogenesis	[39]
4	DLX2	In vitro	Promotes osteogenic activity	DLX2 binds to WNT1, upregulating WNT1 transcription and activating the Wnt/β-catenin signaling pathway	[40]
5	FOXQ1	In vitro and in vivo	Promotes osteogenic activity	FOXQ1 regulates the activities of Wnt/β-catenin pathway by binding to annexin A2	[41]
6	BRD4	In vitro	Promotes osteogenic activity	BRD4 improves the expression of Wnt3a and β-catenin by binding to the promoter region of Wnt3a or β-catenin during osteogenic differentiation in BMSCs	[42]
7	LECT2	In vitro and in vivo	Negatively regulates osteogenic activity	LECT2 knockdown triggers the Wnt/β-catenin pathway, promoting the osteoblast differentiation of MSCs	[43]

CRYAB: Alpha-crystallin B chain; LGR6: Leucine-rich repeat-containing G protein-coupled receptor 6; KLF14: Kruppel-like factor 14; DLX2: Distal-less homeobox 2; FOXQ1: Forkhead box Q1; BRD4: Bromodomain 4; LECT2: Leukocyte cell-derived chemotaxin 2; BMSC: Bone marrow stem cells.

Table 2 Molecules regulating osteogenesis via the bone morphogenetic protein/Smad-dependent pathway

No	Name	Experimental model(s)	Effect	Role	Ref.
1	LMCD1	In vitro and in vivo	Promotes osteogenic activity	Acts along with Smad-specific E3 ubiquitin protein ligase 1 to modulate the ubiquitination levels of Smad1 and Runx2	[50]
2	Carnosol	In vitro	Induces osteogenic activity	Stimulates osteogenesis via the activation of the BMP signaling pathway and consequent upregulation of the expression of downstream target genes	[51]
3	IL-1β	In vitro and in vivo	Promotes osteogenic activity	Enhances the osteogenic differentiation potential of mouse bone marrow MSCs by activating the BMP/Smad osteogenic signaling pathway	[52]
4	NGF	In vitro	Promotes osteogenic activity	Increases BMP2 expression and phosphorylation and nuclear translocation of Smad1/5/8	[53]
5	Nobiletin	In vitro	Promotes osteogenic activity	Stimulates osteogenic differentiation by promoting Runx2 and BMP2 signaling	[54]
6	Simvastatin	In vitro and in vivo	Promotes osteogenic activity	Increases the expression of osteogenic differentiation- and BMP2/Smads pathway-associated genes	[55]
7	Isoquercitrin	In vitro	Promotes osteogenic activity	Stimulates osteogenic differentiation via Runx2 expression in osteoblasts and BMP pathway in BMSCs	[56]

LMCD1: LIM- and cysteine-rich domains 1; IL-1β: Interleukin-1β; NGF: Nerve growth factor; Runx2: Runx family transcription factor 2; BMSC: Bone marrow stem cells; BMP: Bone morphogenetic protein; MSCs: Mesenchymal stem cells.