Studies have linked Wnt/β-catenin signaling to degenerative joint disease in humans and mice.19,23,38–43 The fact that Col2-cre-mediated deletion of Lrp5 results in normal appearing knee joints is not surprising given that global deletion of Lrp5 was previously shown to not alter skeletal morphogenesis.25,44–46 However, homozygosity for an inactivating allele of Lrp6 results in neonatal lethality,24 so it was previously not possible to evaluate the effects of loss of Lrp6 on the adult knee. Here, LRP5 is linked to osteoarthritis.