Table 1.

Summary of Bone Phenotypes in Genetic Models of Altered Wnt Signaling

Gene	Role in Wnt pathway(s)	Bone Phenotype(s)*	References
APC	Downregulates of β-catenin signaling	CKO: Increased BMD	[91, 92]
Axin2	Downregulates of β-catenin signaling	CKO: Craniosynostosis; Increased BMD	[93, 94]
β-Catenin	Interacts with Lef1/Tcfs to regulate gene expression	CKO: Ectopic formation of chondrocytes	[21–23]
		Tg: Increased ossification, suppression of chondrocytes	[20, 24]
Dkk1	Inhibits β-catenin signaling	Het: High bone mass	[47]
		Tg: Low bone mass	[46]
Dkk2	Inhibits β-catenin signaling	KO: Low bone mass	[95]
		Het: Normal
Fzd9	Receptor for Wnts	KO: Decreased bone formation; Osteopenic	[96]
GSK3β	Inhibits β-catenin signaling by targeting β-catenin for degradation	Het: Increased bone formation	[97]
		Pharmacological inhibition: Increased BMD	[31]
Krm1/2	Potentiate capacity of Dkks to inhibit β-catenin signaling	CKO: Increases BMD	[49]
Lrp5	Co-receptor for Wnts	KO: Decreased BMD	[13]
		CKO (Osteoblasts): Normal	[19]
		CKO (Duodenum): Low BMD
		GOF: Increased BMD	[15, 16]
Lrp6	Co-receptor for Wnts	CKO: Decreased BMD	[98]
Sfrp1	Secreted inhibitor of β-catenin signaling	KO: Increased BMD	[76]
SOST	Inhibits β-catenin signaling	KO: Increased BMD	[61]
		Tg: Osteopenic	[62]
Tcf7 (Tcf1)	Transcription factor activated through interaction with β-catenin	DKO (Tcf7−/−Lef1−/−): Similar to Wnt3a−/− phenotype	[99]
		KO: Low bone mass, increase in bone resorption	[20]
Wnt3a	Activates β-catenin pathway	Het: No change in BMD	[25]
Wnt5a	Activates β-catenin and noncanonical pathways	Het: Reduced BMD, increased adipogenesis	[25]
Wnt10b	Activates β-catenin	KO: Reduced BMD, increased adipogenesis	[26, 27]
		Tg: Increased BMD

^*BMD: bone mineral density; CKO: conditional knockout mouse; Het: heterozygous knockout mouse; KO: global knockout; DKO: double global knockout; Tg: transgenic; GOF: gain of function