Regulation of osteoblast behaviors via cross-talk between Hippo/YAP and MAPK signaling pathway under fluoride exposure

This study evaluated the role of Hippo/YAP and MAPK signaling pathway in osteoblast behaviors under excessive fluoride exposure in vitro and in vivo. Commercially pure Ti (cp-Ti) samples were exposed to fluoride (0, 0.1, and 1.0  mM NaF) for 7 days. Cell adhesion was observed using a laser scanning confocal microscope. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, respectively. The expressions of osteoblast markers and key molecules in MAPK and YAP pathway were detected by Western blot. In vivo studies were evaluated by histology methods in C57/BL6 mice model. Our results showed that 1.0 mM NaF destroyed the passivation film on cp-Ti surface, which further inhibited the osteoblast adhesion and spreading. Meanwhile, compared to other groups, 1.0 mM NaF led to a remarkable reduction in cell viability (P <  0.05), as well as increased apoptosis (P <  0.05) and downregulation of osteogenesis protein expression (P <  0.05). MAPK and YAP signaling pathways were also activated under 1.0 mM NaF exposure, and JNK seemed to regulate YAP phosphorylation in response to NaF impacts on osteoblasts. In vivo fluorosis mouse model further indicated that 100 ppm NaF group (high fluoride group) increased bone resorption and inhibited the nuclear translocation of YAP. The osteoblast behaviors were negatively altered under excessive fluoride, and MAPK/JNK axis contributed to YAP signaling activation in regulating NaF-induced osteoblast b...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research