Given that little information is known regarding the role of the COX2/PGE2/EP2 signaling pathway in the pathogenesis of DMD, the aim of this study was to investigate the role of the prostaglandin E 2/prostaglandin E 2 receptor 2 (PGE2/EP2) signaling pathway, including enzymes that catabolize the production of PGE2 and degrade PGE2 and their receptor’s expression, and its involvement in the development of muscle pathology (including HO) in DKO-Hom mice and to determine if targeting the PGE2/EP2 signaling pathway can improve the pathology of muscular dystrophic muscle and bone health. Here, PTGER2 is linked to Duchenne muscular dystrophy.