Sodium fluoride influences the expression of keratins in cultured keratinocytes.

Epithelia in lung, skin, and kidney are often exposed to fluoride, and tissue damage in lung and kidney due to fluoride is well documented. Nevertheless, the biological effects of fluoride on epithelia are poorly investigated. In the present study, we report effects of sodium fluoride (NaF) on the differentiation of a human epithelial cell line, HaCaT. These cells may serve as a keratinocyte model, because they express a wide spectrum of keratins (Ks), and they associate into stratified tissue-like arrangements along with changes in their keratin pattern. NaF was added to the culture medium at concentrations of 0.5 and 5 mM. Cell proliferation remained intact, but cell functions were altered at high dose, and HSP70 was induced. Reverse transcription-polymerase chain reaction and Western blotting revealed that keratin (K) 15 mRNA and protein expression, associated with stratification of epithelia, were inhibited. Also, expression of keratins typical for terminal differentiation, K1 and K10, was decreased and so was the expression of the K1/10 regulating enhancer binding protein c/EBP alpha. Stratification of HaCaT cells was abolished at high fluoride dose, as assessed by electron microscopy. The changes in keratin expression were not reversed by withdrawal of fluoride. Taken together, NaF at high dose blocked terminal differentiation of HaCaT cells, visible by keratin expression and failing stratification. This effect may disturb tissue formation due to altered cell interactions.

Nasal inverted papilloma expresses the muscle segment homeobox gene Msx2: possible prognostic implications.

Nasal inverted papilloma is a rare benign tumor of epithelial origin with aggressive evolution, bone destruction, recurrence, and malignant transformation. Msx2 is a homeobox gene implicated in organ development, bone metabolism, and tumorigenesis. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry, Msx2 expression was examined in nasal inverted papilloma and in nontumorigenic tissue counterparts. For the first time, Msx2 was detected in all inverted papillomas but not in the nasal polyps or in the normal mucosa. The protein expression level was directly and significantly associated with tumor recurrence. Furthermore, Msx2 was associated with bone resorption markers receptor activator of nuclear factor-kappa B ligand and tartrate-resistant acid phosphatase, suggesting a role in osteolysis. In conclusion, Msx2 expression may represent a useful prognostic marker in inverted papilloma.