Macrophage-Bmp5 Axis Regulates Oral Leukoplakia Carcinogenesis

The aim of this study was to investigate the critical role of macrophage-BMP5 aixs in the carcinogenesis of oral leukoplakia (OLK). In a mouse model of oral leukoplakia (OLK) depleted of macrophages, macro assessment of oral lesions, histopathological analysis of tongue tissue, immunophenotyping, TUNEL assay for apoptotic quantification, RT-qPCR/Western blot validation, and transcriptome analysis were comprehensivly conducted. Target gene identification was achieved through comparative analysis of transcriptome sequencing data, pinpointing BMP5 as a critical regulator. The association between macrophage infiltration levels and BMP5 expression was validated by integrating experimental datasets with publicly accessible clinical databases. Leuk1 cells were transfected with lentiviral vectors to induce overexpression and knockdown of BMP5, and the effects of BMP5 on cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) were systematically characterized. In vivo functional validation was achieved through localized administration of recombinant BMP5 protein via tongue submucosal injection in the murine leukoplakia model. Finally, we utilized tongue tip-targeted siRNA delivery to verify the role of BMP5 in macrophage-mediated regulatory networks. The expression of the target gene BMP5 was significantly upregulated after macrophage depletion. This up-regulation inhibits the proliferation of cells, promotes apoptosis, and reverses the epithelial-mesenchymal transition (EMT) process, thereby blocking the carcinogenesisof OLK and potentially reversing its progression. The knockdown of BMP5 reversed the protective effect associated with macrophage depletion. The macrophage-BMP5 axis inhibits the carcinogenesis of OLK through modulation of cellular proliferation, apoptosis, and EMT.