TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts.
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-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Chiaki
C
Yamada
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Tomonao
T
Aikawa
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Emi
E
Okuno
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Kazuaki
K
Miyagawa
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Katsuhiko
K
Amano
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Sosuke
S
Takahata
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Masaaki
M
Kimata
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Masaya
M
Okura
Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-Ku, Okayama 700-8558, Japan.
Seiji
S
Iida
First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita City, Osaka 565-0871, Japan.
Mikihiko
M
Kogo
D020420:Cyst Fluid / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053582:Interleukin-1alpha / Q000494:pharmacology; D007573:Jaw Neoplasms / Q000378:metabolism* / Q000473:pathology; D009807:Odontogenic Cysts / Q000378:metabolism / Q000473:pathology; D009808:Odontogenic Tumors / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000096:biosynthesis; D053245:RANK Ligand / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D053582:Interleukin-1alpha; D053244:Osteoprotegerin; D053245:RANK Ligand; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1