MMP13 Expression and Activity Suggest Its Role in Bone Resorption in Ameloblastomas

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-08-27 DOI:10.1111/jop.13577

Alline Teixeira Valeriano, Lais Santos Camara, Vanessa de Fátima Bernardes, Fabiano Sviatopolk-Mirsky Pais, Flávio Marcos Gomes Araújo, Anna Christina de Matos Salim, Gabriel da Rocha Fernandes, Fernanda Stussi, Carolina Cavalieri Gomes, Pedro Paulo de Andrade Santos, Lélia Batista de Souza, Ricardo Santiago Gomez, Marina Gonçalves Diniz

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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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MMP13的表达和活性表明其在釉母细胞瘤骨吸收中的作用

背景介绍釉母细胞瘤是一种局部破坏性良性牙源性肿瘤。传统釉母细胞瘤的肿瘤细胞可浸润结缔组织和骨，而单囊性釉母细胞瘤的上皮细胞被包裹。目前尚不清楚驱动绒母细胞瘤骨吸收的机制：采用 RT-qPCR 方法评估了更大范围的传统牙釉质母细胞瘤和单囊性牙釉质母细胞瘤中与骨吸收相关的基因 MMP13 的 mRNA 水平。此外，还对胶原酶 3（由 MMP13 基因编码）的酶切凝胶和免疫表达谱进行了评估：结果：在母细胞瘤中观察到与骨矿化有关的丰富通路和 MMP13 的上调。在肿瘤裂解液中检测到胶原酶 3 的胶原溶解活性。在浸润单囊性母细胞瘤纤维囊的母细胞瘤上皮中观察到胶原酶 3 免疫阳性。在肿瘤-骨界面，基质细胞、成骨细胞和骨细胞中均检测到胶原酶 3 的表达：结论：研究结果表明，MMP13可能参与了与成骨细胞瘤相关的骨吸收和进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464