TGF in jaw tumor fluids induces RANKL expression in stromal fibroblasts

Chiaki Yamada, Tomonao Aikawa, Emi Okuno, Kazuaki Miyagawa, Katsuhiko Amano, Sosuke Takahata, Masaaki Kimata, Masaya Okura, Seiji Iida, Mikihiko Kogo

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-(TGF-), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-B ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1 (IL-1) signaling and non-COX-2/PGE2 pathway through TGF receptor signaling. TGF-1 and IL-1 produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalInternational journal of oncology
Issue number2
Publication statusPublished - Aug 2016


  • Interleukin-1
  • Keratocystic odontogenic tumor
  • Odontogenic tumor
  • Receptor activator of NF-B ligand
  • Transforming growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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