title: Oral squamous cell carcinoma cells induce osteoclast differentiation by suppression of osteoprotegerin expression in osteoblasts.
abstract: The invasion of oral squamous cell carcinoma (SCC) cells into the mandibular bone is a common clinical problem. It has been reported that BHY cells, a human oral SCC cell line, are capable of invading mandibular bone of nude mice. These results led us to examine possible mechanisms of osteoclastogenesis induced by BHY cells using in vitro culture systems. When BHY cells were cocultured with mouse bone marrow cells (BMCs), only few osteoclasts were formed, even though BHY cells express the receptor activator of NF-kappaB ligand (RANKL). However, adding BHY cells to a coculture of mouse primary osteoblasts (POBs) and BMCs markedly induced osteoclastogenesis in the absence of osteotropic factors. Furthermore, another oral SCC cell line, HSC-2, which does not express RANKL, also induced osteoclastogenesis in our cocultures. These effects were significantly, but not completely, inhibited by adding osteoprotegerin (OPG). In addition, we also found that TNFalpha released from these cells partially contributes to osteoclastogenesis via a RANKL-independent mechanism. Adding BHY or HSC-2 cells suppressed mouse OPG mRNA expression and protein production by POBs in cocultures of POBs and human oral SCC cells. This finding is consistent with the result that BHY cells and HSC-2 cells did not enhance osteoclastogenesis in cocultures of BMCs and POBs from OPG-deficient mice. Immunohistochemical analysis showed a reduction of OPG expression in osteolytic lesions as compared to normal lesions from oral SCC patients. Therefore, oral SCC-induced suppression of OPG expression in POBs appears critical for osteoclastogenesis, rather than expression of RANKL in SCC cells.
authors.affiliation: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Tada
authors.forename: Eijiro
authors.initials: E
authors.lastname: Jimi
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Ozeki
authors.forename: Koji
authors.initials: K
authors.lastname: Okabe
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology; D002450:Cell Communication; D002454:Cell Differentiation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha