ACAN and osteoporosis: LRP5 knockout mice develop severe osteoporosis, resembling human osteoporosis–pseudoglioma syndrome (OPPG); this phenotype arises from the disruption of Wnt3a-mediated Axin-2 expression, reduced bone mineralization, and increased expression of chondrocyte differentiation markers (Collagen II, Aggrecan, Collagen X, and Sox9), leading to the diversion of the osteoblast lineage to the chondrocyte lineage [13].