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MMP13 EXPRESSION AND ACTIVITY SUGGEST ITS ROLE IN BONE RESORPTION IN AMELOBLASTOMAS
Author
Valeriano, Alline Teixeira
Camara, Lais Santos
Bernardes, Vanessa de Fátima
Pais, Fabiano Sviatopolk-Mirsky
Araújo, Flávio Marcos Gomes
Salim, Anna Christina de Matos
Fernandes, Gabriel da Rocha
Stussi, Fernanda
Gomes, Carolina Cavalieri
Santos, Pedro Paulo de Andrade
Souza, Lélia Batista de
Gomez, Ricardo Santiago
Diniz, Marina Gonçalves
Camara, Lais Santos
Bernardes, Vanessa de Fátima
Pais, Fabiano Sviatopolk-Mirsky
Araújo, Flávio Marcos Gomes
Salim, Anna Christina de Matos
Fernandes, Gabriel da Rocha
Stussi, Fernanda
Gomes, Carolina Cavalieri
Santos, Pedro Paulo de Andrade
Souza, Lélia Batista de
Gomez, Ricardo Santiago
Diniz, Marina Gonçalves
Affilliation
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Universidade Federal do Rio Grande do Norte. Department of Morphology. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Department of Oral Pathology. Natal, RN, Brasil.
Universidade Federal de Minas Gerais. School of Dentistry. Department of Oral Surgery and Pathology. Belo Horizonte, MG, Brasil / Faculdade Ciências Médicas de Minas Gerais. Medical School. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Universidade Federal do Rio Grande do Norte. Department of Morphology. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Department of Oral Pathology. Natal, RN, Brasil.
Universidade Federal de Minas Gerais. School of Dentistry. Department of Oral Surgery and Pathology. Belo Horizonte, MG, Brasil / Faculdade Ciências Médicas de Minas Gerais. Medical School. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Biological Sciences Institute. Department of Pathology. Belo Horizonte, MG, Brasil.
Abstract
Background: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. Methods: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. Results: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor–bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. Conclusion: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression.
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