Role of connexin 43 in odontogenesis and odontogenic tumors.

Abstract

Connexin 43 (Cx43) is a transmembrane protein forming gap junctions essential for intercellular communication, regulating ion and molecule exchange, and coordinating key developmental and pathological processes. In odontogenesis, Cx43 expression in ameloblasts and odontoblasts orchestrates differentiation, mineralization, and tissue repair. Its dynamic regulation influences enamel and dentin formation, while altered expression is linked to defective tooth development. Beyond dental tissues, Cx43 participates in craniofacial morphogenesis and bone remodeling. In odontogenic tumors, Cx43 shows heterogeneous expression patterns, reflecting its role in tumor architecture, differentiation, and aggressiveness. High mesenchymal expression is seen in ameloblastic fibromas and fibro-odontomas, whereas follicular ameloblastomas and odontogenic keratocysts exhibit downregulation, particularly in basal cells-correlating with increased proliferation, anti-apoptosis, and autophagy markers. These variations in odontogenic tumors suggest that Cx43 may act as a tumor suppressor by maintaining epithelial organization and regulating cell polarity. Molecularly, Cx43 interacts with MAPK/ERK, PI3K/AKT, and Wnt/β-catenin pathways, influencing cell cycle control, apoptosis, and epithelial-mesenchymal interactions. Loss of Cx43 disrupts gap junctional intercellular communication, potentially enhancing tumor progression. Therapeutically, modulating Cx43 could inhibit tumor angiogenesis, restore normal growth control, and promote differentiation toward less aggressive phenotypes. However, given its dual role in tumor suppression and tissue repair, targeted interventions must be context-specific. Cx43 emerges as a promising diagnostic, prognostic, and therapeutic biomarker in different neoplasias, warranting further investigation to optimize clinical applications. The objective of this work is to review current information on the role of CX43 in normal tissue and odontogenic tumors to evaluate its possible usefulness as a future therapeutic target.