Advertisement

Expression of bone resorption regulators (RANK, RANKL, and OPG) in odontogenic tumors

      Objective

      To investigate the expression of bone resorption regulators (receptor activator of nuclear factor kappa B [RANK], RANK ligand [RANKL], and osteoprotegerin [OPG]) in calcifying cystic odontogenic tumor (CCOT), adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor (CEOT), odontogenic myxoma (OM), and ameloblastic fibroma (AF).

      Study design

      The expression of these mediators was evaluated by means of immunohistochemistry.

      Results

      All specimens demonstrated positive immunoreactivity to RANK, RANKL, and OPG. The quantification of these mediators in epithelium revealed a similar pattern of expression for RANKL and OPG in CCOT, AOT, CEOT, and AF. With regard to stromal/mesenchymal cells, the majority of AOT and CCOT cases showed a higher content of OPG than RANKL, whereas CEOT, OM, and especially AF had a tendency to present a greater content of RANKL than OPG.

      Conclusion

      Our data indicate that the CCOT, AOT, CEOT, OM, and AF cell constituents express key regulators of bone metabolism that might locally modulate tumor-associated bone resorption.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      References

        • Buchner A.
        • Merrell P.W.
        • Carpenter W.M.
        Relative frequency of central odontogenic tumors: a study of 1,088 cases from northern California and comparison to studies from other parts of the world.
        J Oral Maxillofac Surg. 2006; 64: 1343-1352
        • Jing W.
        • Xuan M.
        • Lin Y.
        • Wu L.
        • Liu L.
        • Zheng X.
        • et al.
        Odontogenic tumours: a retrospective study of 1642 cases in a Chinese population.
        Int J Oral Maxillofac Surg. 2007; 36: 20-25
        • Prætorius F.
        • Ledesma-Montes C.
        Calcifying cystic odontogenic tumour.
        in: Barnes L. Eveson J.W. Reichart P. Sindransky D. Pathology and genetics of head and neck tumors World Health Organization classification of tumours. IARC Press, Lyon2005: 313
        • Philipsen H.P.
        • Nikai H.
        Adenomatoid odontogenic tumour.
        in: Barnes L. Eveson J.W. Reichart P. Sindransky D. Pathology and genetics of head and neck tumors World Health Organization classification of tumours. IARC Press, Lyon2005: 305
        • Slootweg P.J.
        Ameloblastic fibroma/fibrodentinoma.
        in: Barnes L. Eveson J.W. Reichart P. Sindransky D. Pathology and genetics of head and neck tumors World Health Organization classification of tumours. IARC Press, Lyon2005: 308
        • Takata T.
        • Slootweg P.J.
        Calcifying epithelial odontogenic tumour.
        in: Barnes L. Eveson J.W. Reichart P. Sindransky D. Pathology and genetics of head and neck tumors World Health Organization classification of tumours. IARC Press, Lyon2005: 302-303
        • Buchner A.
        • Odell E.W.
        Odontogenic myxoma/myxofibroma.
        in: Barnes L. Eveson J.W. Reichart P. Sindransky D. Pathology and genetics of head and neck tumors World Health Organization classification of tumours. IARC Press, Lyon2005: 316-317
        • Regezi J.A.
        Odontogenic cysts, odontogenic tumors, fibroosseous, and giant cell lesions of the jaws.
        Mod Pathol. 2002; 15: 331-341
        • Li T.J.
        • Yu S.F.
        Clinicopathologic spectrum of the so-called calcifying odontogenic cysts.
        Am J Surg Pathol. 2003; 27: 372-384
        • Noffke C.E.E.
        • Raubenheimer E.J.
        • Chabikuli N.J.
        • Bouckaert M.R.M.
        Odontogenic myxoma: review of the literature and report of 30 cases from South Africa.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104: 101-109
        • Chen Y.
        • Wang J.M.
        • Li T.J.
        Ameloblastic fibroma: a review of published studies with special reference to its nature and biologic behavior.
        Oral Oncol. 2007; 43: 960-969
        • Shetty K.
        • Vastardis S.
        • Giannini P.
        Management of an unusually large adenomatoid odontogenic tumor.
        Oral Oncol. 2005; 41: 316-318
        • Mohtasham N.
        • Habibi A.
        • Jafarzadeh H.
        • Amirchaghmaghi M.
        Extension of Pindborg tumor to the maxillary sinus: a case report.
        J Oral Pathol Med. 2008; 37: 59-61
        • Lerner U.H.
        New molecules in the tumor necrosis factor ligand and receptor superfamilies with importance for physiological and pathological bone resorption.
        Crit Rev Oral Biol Med. 2004; 15: 64-81
        • Blair J.M.
        • Zheng Y.
        • Dunstan C.R.
        RANK ligand.
        Int J Biochem Cell Biol. 2007; 39: 1077-1081
        • Rani C.S.S.
        • MacDougall M.
        Dental cells express factors that regulate bone resorption.
        Mol Cell Biol Res Commun. 2000; 3: 145-152
        • Takayanagi H.
        Inflammatory bone destruction and osteoimmunology.
        J. Periodont Res. 2005; 40: 287-293
        • Page G.
        • Miossec P.
        RANK and RANKL expression as markers of dendritic cell-T cell interactions in paired samples of rheumatoid synovium and lymph nodes.
        Arthritis Rheum. 2005; 52: 2307-2312
        • Tobón-Arroyave S.I.
        • Franco-González L.M.
        • Isaza-Guzmán D.M.
        • Floréz-Moreno G.A.
        • Bravo-Vásquez T.
        • Castañeda-Peláez D.A.
        • et al.
        Immunohistochemical expression of RANK, GRalpha and CTR in central giant cell granuloma of the jaws.
        Oral Oncol. 2005; 41: 480-488
        • Anderson D.M.
        • Maraskovsky E.
        • Billingsley W.L.
        • Dougall W.C.
        • Tometsko M.E.
        • Roux E.R.
        • et al.
        A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
        Nature. 1997; 390: 175-179
        • Silva T.A.
        • Batista A.C.
        • Mendonça E.F.
        • Leles C.R.
        • Fukada S.
        • Cunha F.Q.
        Comparative expression of RANK, RANKL, and OPG in keratocystic odontogenic tumors, ameloblastomas, and dentigerous cysts.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 105: 333-341
        • Boyle W.J.
        • Simonet W.S.
        • Lacey D.L.
        Osteoclast differentiation and activation.
        Nature. 2003; 423: 337-342
        • Belibasakis G.N.
        • Bostanci N.
        • Hashim A.
        • Johansson A.
        • Aduse-Opoku J.
        • Curtis M.A.
        • et al.
        Regulation of RANKL and OPG gene expression in human gengival fibroblast and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains.
        Microb Pathog. 2007; 43: 46-53
        • Tay J.Y.
        • Bay B.H.
        • Yeo J.F.
        • Harris M.
        • Meghji S.
        • Dheen S.T.
        Identification of RANKL in osteolytic lesions of the facial skeleton.
        J Dent Res. 2004; 83: 349-353
        • Kumamoto H.
        • Ooya K.
        Expression of parathyroid hormone–related protein (PTHrP), osteoclast differentiation factor (ODF)/receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoclastogenesis inhibitory factor (OCIF)/osteoprotegerin (OPG) in ameloblastomas.
        J Oral Pathol Med. 2004; 33: 46-52
        • Sandra F.
        • Hendarmin L.
        • Kukita T.
        • Nakao Y.
        • Nakamura N.
        • Nakamura S.
        Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone.
        Oral Oncol. 2005; 41: 637-644
        • Wittrant Y.
        • Théoleyre S.
        • Chipoy C.
        • Padrines M.
        • Blanchard F.
        • Heymann D.
        • et al.
        RANK/RANKL/OPG: new therapeutic targets in bone tumours and associated osteolysis.
        Biochim Biophys Acta. 2004; 1704: 49-57
        • Wise G.E.
        • Lumpkin S.J.
        • Huang H.
        • Zhang Q.
        Osteoprotegerin and osteoclasts differentiation factor in tooth eruption.
        J Dent Res. 2000; 79: 1937-1942
        • Menezes R.
        • Bramante C.M.
        • Silva-Paiva K.B.
        • Letra A.
        • Carneiro E.
        • Fernando-Zambuzzi W.
        • et al.
        Receptor activator NFkappaB-ligand and osteoprotegerin protein expression in human periapical cysts and granulomas.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102: 404-409
        • Vernal R.
        • Dezerega A.
        • Dutzan N.
        • Chaparro A.
        • León R.
        • Chandía S.
        • et al.
        RANKL in human periapical granuloma: possible involvement in periapical bone destruction.
        Oral Dis. 2006; 12: 283-289
        • Sandra F.
        • Hendarmin L.
        • Nakamura S.
        Osteoprotegerin (OPG) binds with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): suppression of TRAIL-induced apoptosis in ameloblastomas.
        Oral Oncol. 2006; 42: 415-420
        • Zakopoulos A.
        • Tosios K.I.
        • Vlachodimitropoulos D.
        Expression of OPG, RANKL, and TRAIL in odontogenic keratocysts (OKC): an immunohistochemical study.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 103: e24
        • Fernandes A.M.
        • Duarte E.C.
        • Pimenta F.J.
        • Souza L.N.
        • Santos V.R.
        • Mesquita R.A.
        • et al.
        Odontogenic tumors: a study of 340 cases in a Brazilian population.
        J Oral Pathol Med. 2005; 34: 483-487
        • Jones A.V.
        • Franklin C.D.
        An analysis of oral and maxillofacial pathology found in adults over a 30-year period.
        J Oral Pathol Med. 2006; 35: 392-401
        • Steeve K.T.
        • Marc P.
        • Sandrine T.
        • Heymann D.
        • Yannick F.
        IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology.
        Cytokine Growth Factor Rev. 2004; 15: 49-60
        • Khosla S.
        Minireview: the OPG/RANKL/RANK system.
        Endocrinology. 2001; 142: 5055
        • Wada T.
        • Nakashima T.
        • Hiroshi N.
        • Penninger J.M.
        RANKL-RANK signaling in osteoclastogenesis and bone disease.
        Trends Mol Med. 2006; 12: 17-25