Family with sequence similarity 20-member C (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100 secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands.
Fam20c
f/f
;
Mmtv-Cre
mice were created in which
Fam20c
was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross-sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of β nerve growth factor, α-amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na
+
, Cl
−
and K
+
concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore,
Fam20c
deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia.
Bone damage results from the imbalance of bone homeostasis maintained by osteoblast-regulated bone formation and osteoclast-mediated bone resorption. Conventional drug therapy and gene therapy may not optimally regulate the bone remodeling process due to the unitary pharmacological mechanism of drug and the safety and targeting of gene vectors. In the present study, multifunctional fluorescent alendronate-polyethyleneimine carbon dots (Alen-PEI CDs) are innovatively synthesized, which have excellent biocompatibility, selective bone targeting, gene carrying capacity, and anti-bone absorption effect. As gene vectors, bone morphogenic protein 2 (BMP2) gene-loaded Alen-PEI CDs greatly enhance osteoblast differentiation and bone regeneration. Notably, Alen-PEI CDs are found to directly inhibit the formation and function of osteoclasts, effectively attenuating the LPS-induced skull osteolysis in mice. Furthermore, their cumulative toxicity is lower than that of Alen, indicating their potential as an anti-bone resorptive nanodrug. These results show that the bone-targeting Alen-PEI CDs significantly reverse the imbalance of bone homeostasis through a dual-directional mechanism-directly suppressing bone resorption and indirectly inducing bone formation by transfection of osteogenic therapeutic genes. Overall, the study expands the application for carbon dots in biomedicine, providing new insights for the further development of novel selectively targeted multifunctional nanodrugs for the treatment of bone-destructive diseases.
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