Simultaneous activation and reciprocal inhibition of β-catenin– and CaMKII–dependent pathways in AHACs. (A and B) In AHACs, WNT-3A up-regulates AXIN2 expression and proliferation through the Wnt canonical pathway (A), but induces loss of differentiation via a G protein–mediated Ca²⁺/CaMKII–dependent pathway (B). (C–E) These two pathways are reciprocally inhibitory and in equilibrium. Therefore, either exogenous WNT-3A (C) or blockade of the canonical pathway with DKK1 (D–E) will both result in loss of chondrocyte phenotype.