Stable states of the PTHrP mutant networks.

The values of nodes representing growth factors and transcription factors are tabled for the relevant stable states in the mutant growth plate. The presence of paracrine signalling is indicated in the table (ext). For the PTHrP null network, the resting zone situation is unchanged, save for PTHrP secretion. However, a stable proliferative state is nonexistent and a state of hypertrophy is reached instead. By calculating the state transition graph a Sox9 positive state can be detected. In a network with constitutively active PPR (PTHrP+/PPR+), the resting zone is identical to the wild type situation. The proliferative zone is also unaffected. However, no hypertrophy is reached as the PTHrP pathway remains active and hence blocks chondrocyte differentiation. Hypertrophy might be reached if PTHrP signalling is diminished.