Bone Resorption in Ameloblastoma and Its Underlying Mechanism

Jackson Jackson, Johni Halim, Rezky Anggraeni, Ferry Sandra


Ameloblastoma, a tumor located in the jaw, grows slowly but locally invasive. Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-α. RANKL plays an important role in generating osteoclastogenesis. MMPs degrade the extracellular matrix. TNF-α can induce the formation of osteoclast and modulate the MMPs. In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed.

Keywords: Ameloblastoma, RANKL, MMPs, TNF-α.

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Al-Rawi, N.H., Al-Siraj, A.K. and Majeed, A.H., 2018, Comparison of osteoclastogenesis and local invasiveness of ameloblastoma keratocystic odontogenic tumor, Eur. J. Dent., 12(1), 36-42. CrossRef

Amirhosseini, M., Madsen, R.V., Escott, K.J., Bostrom, M.P., Ross, F.P. and Fahlgren, A., 2018, GSK-3β Inhibition Suppresses Instability-induced Osteolysis by a Dual Action on Osteoblast and Osteoclast Differentiation,J. Cell. Physiol., 233(3), 2398–2408. CrossRef

Anne, R., Krisnuhoni, E., Chotimah, C. and Latief, B.S., 2014, Matrix metalloproteinase-9 (MMP-9) expression in different subtypes of ameloblastoma, J. Maxillofac. Oral. Surg., 13(3), 281–285. CrossRef

Antonoglou, G.N. and Sandor, G.K., 2015, Recurrence rates of intraosseous ameloblastomas of the jaws: A systematic review of conservative versus aggressive treatment approaches and meta‐analysis of non‐randomized studies, Journal of Cranio‐Maxillo‐Facial Surgery, 43(1), 149–157. CrossRef

Arora, S., 2015, Unicystic ameloblastoma: A perception for the cautious interpretation of radiographic and histologic findings, J. Coll. Physician. Surg. Park., 25(10), 761-764. CrossRef

Brown, N.A., Betz, B.L., Weigelin, H.C., Elenitoba-Johnson, K.S., Lim, M.S. and Bailey, N.G., 2015, Evaluation of allele-specific PCR and immunohistochemistry for the detection of BRAF V600E mutations in hairy cell leukemia, Am. J. Clin. Pathol., 143(1), 89–99. CrossRef

Dissanayake, R.K., Jayasooriya, P.R., Siriwardena, D.J. and Tilakaratne W.M., 2011, Review of metastasizing (malignant) ameloblastoma (METAM): pattern of metastasis and treatment, Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod., 111(6), 734-41. CrossRef

Effiom, O.A., Ogundana, O.M., Akinshipo, A.O. and Akintoye, S.O., 2018, Ameloblastoma: current etiopathological concepts and management, Oral. Diseases., 24(3), 307–316. CrossRef

Feng, W., Guo, J. and Li, M., 2019, RANKL-independent modulation of osteoclastogenesis, J. Oral. Biosci, 61(1),16-21. CrossRef

Figueiredo, N.R., Dinkar, A.D., Meena, M., Sujata, S. and Manisha, K., 2014, Ameloblastoma: A clinicoradiographic and histopathologic correlation of 11 cases seen in Goa during 2008-2012, Contemp. Clin. Dent., 5(2), 16-165. CrossRef

França, L.J., Curioni, O.A., Paiva, D.L., Vianna, D.M., Dedivitis, R.A. and Rapoport, A., 2012, Ameloblastoma demographic, clinical, and treatment study: analysis of 40 cases, Braz. J. Otorhinolaryngol., 78(3), 38-41. CrossRef

Fuchigami, T., Kibe, T., Koyama, H., Kishida, S., Iijima, M., Nishizawa, Y., et al., 2014, Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma, Biochem. Biophys. Res. Commun., 451, 491–496. CrossRef

Gomes, C.C., Duarte, A.P., Diniz, M.G. and Gomez, R.S., 2010, Current concepts of ameloblastoma pathogenesis, J. Oral. Pathol. Med., 39, 585-591. CrossRef

Hendra, F.N., Natsir-Kalla, D.S., Van-Cann, E.M., de-Vet, H., Helder, M.N. and Forouzanfar, T., 2019, Radical vs. conservative treatment of intraosseous ameloblastoma: Systematic review and meta-analysis, Oral. Diseases., 25(7), 1683–1696. CrossRef

Hendarmin, L., Sandra, F., Nakao, Y., Ohishi, M. and Nakamura, N., 2005, TNFalpha played a role in the induction of Akt and MAPK signals in ameloblastoma, Oral. Oncol., 41(4), 375-82.

Intapa, C., 2017, Analysis of Prevalence and Clinical Features of Ameloblastoma and its Histopathological Subtypes in Southeast Myanmar and Lower Northern Thailand Populations: A 13-Year Retrospective Study, J. Clin. Diagn. Res., 11(1), ZC102-ZC106. CrossRef

Kamboj, M., Shreedhar, B. and Chaturvedi, M., 2015, Plexiform unicystic ameloblastoma: A case report and data analysis in the Indian population, J. Maxillofac. Oral. Surg., 14(1), 407-411. CrossRef

Kibe, T., Fuchigami, T., Kishida, M., Iijima, M., Ishihata, K., Hijioka, H., et al., 2013, A novel ameloblastoma cell line (AM-3) secretes MMP-9 in response to Wnt-3a and induces osteoclastogenesis, Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol., 115(6), 780–788. CrossRef

Kim, S. and Jang, H., 2001, Ameloblastoma: A clinical, radiographic, and histopathologic analysis of 71 cases, Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod., 91, 649-653. CrossRef

Kreppel, M. and Zoller, J., 2018, Ameloblastoma-clinical, radiological, and therapeutic findings, Oral. Dis., 24(1-2), 63-66. CrossRef

Liu, X., Chen, Z., Lan, T., Liang, P. and Tao, Q., 2019, Upregulation of interleukin-8 and activin A induces osteoclastogenesis in ameloblastoma, Int. J. Mol. Med., 43(6), 2329-2340. CrossRef

Maia, E.C. and Sandrini, F.A.L., 2017, Management techniques of ameloblastoma: a literature review, RGO. Rev. Gaúch. Odontol., 65(1), 62-69. CrossRef

Masthan, K., Anitha, N., Krupaa, J. and Manikkam, S., 2015, Ameloblastoma, J. Pharm. Bioall. Sci., 7, 167-70. CrossRef

McClary, A.C., West, R.B., McClary, A.C., Pollack, J.R., Fischbein, N.J., Holsinger, C.F., et al., 2016, ameloblastoma: a clinical review and trends in management, Eur. Arch. Otorhinolaryngol., 273(7), 1649-1661. CrossRef

More, C., Tailor, M., Patel, H.J., Asrani, M., Thakkar, K. and Adalja, C., 2012, Radiographic analysis of ameloblastoma: a retrospective study, Indian. J. Dent. Res., 23(5), 698. CrossRef

Ohta, K., Naruse, T., Ishida, Y., Shigeishi, H., Nakagawa, T., Fukui, A., et al., 2017, TNF-α-induced IL-6 and MMP-9 expression in immortalized ameloblastoma cell line established by hTERT, Oral. Dis., 23(2), 199-209. CrossRef

Parmar, S., Al-Qamachi, L. and Aga, H., 2016, Ameloblastomas of the mandible and maxilla, Curr. Opin. Otolaryngol. Head. Neck. Surg., 24, 148–154. CrossRef

Petrovic, I.D., Migliacci, J., Ganly, I., Patel, S., Xu, B. and Ghossein, R., et al., 2018, Ameloblastomas of the mandible and maxilla, Ear. Nose. Throat. J., 97(7), E26–E32. CrossRef

Pinheiro, J.J.V., Freitas, V.M., Moretti, A.I.S., Jorge, A.G., Jaeger, R.G., 2004, Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity, Histopathology., 45, 65–72. CrossRef

Qahtani, K.A.L., Alkhudhayri, A.F., Islam, T., Mufargi, K.A.L., Shakweer, W.A.L. and Otaibi, F., 2019, Recurrent unicystic maxillary ameloblastoma presenting as unilateral proptosis, Saudi. J. Ophthalmol., 33(1), 94-98. CrossRef

Qian, Y. and Huang, H.Z., 2010, The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma, J. Oral. Pathol. Med., 39(8), 592-598. CrossRef

Rajendran, R., 2012, cyst and tumors of odontogenic origin. In: Rajendran R, Sivapathasundharam B, ed., 2012, Shafer’s Text Book of Oral Pathology, 7th ed. Indian: Elsevier. pp. 259‑313.

Ruslin, M., Hendra, F.N., Vojdani, A., Hardjosantoso, D., Gazali, M., Tajrin, A., et al., 2018, The Epidemiology, treatment, and complication of ameloblastoma in East-Indonesia: 6 years retrospective study, Med. Oral. Patol. Oral. Cir. Bucal., 23(1), e54–e58. CrossRef

Saghravanian, N., Salehinejad, J., Ghazi, N., Shirdel, M. and Razi, M., 2016, A 40-year Retrospective Clinicopathological Study of Ameloblastoma in Iran, Asian. Pac. J. Cancer. Prev., 17(2), 619-623. CrossRef

Sah, P., Menon, A., Kamath, A., Chandrashekar, C., Carnelio, S. and Radhakrishnan, R., 2013, Role of immunomarkers in the clinicopathological analysis of unicystic ameloblastoma, Dis. Markers., 35(5), 481–488. CrossRef

Sandra, F., Hendarmin, L., Kukita, T., Nakao, Y., Nakamura, N. and Nakamura, S., 2005, Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone, Oral. Oncol., 41(6), 637-644. CrossRef

Sandra, F., Nakamura, N., Mitsuyasu, T., Shiratsuchi, Y. and Ohishi, M., 2001, Two relatively distinct patterns of ameloblastoma: an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (center), Histopathology., 39(1), 93-98. CrossRef

Sandra, F., Mitsuyasu, T., Nakamura, N., Shiratsuchi, Y. and Ohishi, M., 2001, Immunohistochemical evaluation of PCNA and Ki-67 in ameloblastoma, Oral. Oncol., 37(2),193-198. CrossRef

Senguyen, B. and Oygur, T., 2011, Investigation of interleukin-1 alpha and interleukin-6 expression and interleukin-1 alpha gene polymorphism in keratocystic odontogenic tumor and ameloblastomas, Med. Oral. Patol. Oral. Cir. Bucal., 16(4), 467-72. CrossRef

Singh, T., Wiesenfeld, D., Clement, J., Chandu, A. and Nastri, A., 2015, Ameloblastoma: demographic data and treatment outcomes from Melbourne, Australia, Aust. Dent. J., 60(1), 24–29. CrossRef

Siqueira, A.S., Carvalho, M.R.D., Monteiro, A.C.D., Freitas, V.M., Jaeger, R.G. and Pinheiro, J.J.V., 2010, Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behavior, Histopathology., 57(1), 128-137. CrossRef

Sun, T., Yang, W., Toprani, S. M., Guo, W., He, L., DeLeo, A.B., et al., 2020, Correction to Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram, Cell. Commun. Signal., 18(1), 53. CrossRef

Tekkesin, M.S., Mutlu, S. and Olgac, V., 2011, The role of RANK/RANKL/OPG signaling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas, Head. Neck. Pathol., 5(3), 248-253. CrossRef

Toprani, S.M., 2020, DNA damage and repair scenario in ameloblastoma, Oral. Oncol., 108, 104804. CrossRef

Yang, R., Liu, Z., Peng, C., Cao, W. and Ji, T., 2017, Maxillary ameloblastoma: Factors associated with risk of recurrence, Head. & Neck., 39(5), 996–1000. CrossRef

Yang, Z., Li, K., Liang, Q., Zheng, G., Zhang, S., Lao, X., et al., 2018, Elevated hydrostatic pressure promotes ameloblastoma cell invasion through upregulation of MMP-2 and MMP-9 expression via Wnt/β-catenin signaling, J. Oral. Pathol. Med., 47(9), 836-846. CrossRef

Yoshimoto, S., Morita, H., Matsubara, R., Mitsuyasu, T., Imai, Y., Kajioka, S., et al., 2016, Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone, Int. J. Oncol., 48(3), 1258–1270. CrossRef


Copyright (c) 2021 Jackson Jackson, Johni Halim, Rezky Anggraeni, Ferry Sandra

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