Middle ear cholesteatoma is structurally similar to epidermal cyst composed of both stratified squamous epithelium and surrounding fibrosis tissue. In spite of benign tumor, cholesteatoma destructs adjacent bones and causes various complications such as hearing loss, vertigo, facial nerve palsy and brain abscess. In inflammatory bone diseases such as periodontitis and rheumatoid arthritis, receptor activator of nuclear factor κB ligand (RANKL)-mediated osteocalstogenesis is well known to play an important role in bone destruction. Infiltrated leukocytes produce PGE2 which induce RANKL expression in osteoblasts, synovial fibroblasts and gingival fibroblasts. The induction of RANKL is regulated by PGE2-EP4 signaling. On the other hand mechanism of bone destruction by cholesteatoma has been explored for many years, it has not been cleared.
   In this study, we investigated whether RANKL-mediated osteoclastogensis is  in cholesteatoma. We found that PGE2-EP3/4 signaling was important in RANKL expression and osteoclastogensis.

Prostaglandin E2 regulates osteoclastogenesis through the induction of RANKL in middle ear cholesteatoma.