PTGDR2 and osteosarcoma: Some of the pro-apoptotic properties of PGD2 and its metabolites such as 15-deoxy-PGJ2 can be attributed to both PPARγ activation and a receptor-independent mechanism, such as modulation of intracellular redox potential in osteosarcoma cells [114], but a clear contribution of CRTH2-mediated effects is also given: CRTH2 activation can induce apoptosis via autocrine stimulation of both reactive oxygen species and TNF-α production in a MAPK pathway-dependent manner in cardiomyocytes [115], and via Erk1/2 and Akt signaling in human osteoclasts [77].