ABSTRACT
Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin (IL)-1β, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor κB ligand) and macrophage colony-stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.
Subject(s)
Animals , Male , Rats , Acid Phosphatase , Alveolar Bone Loss , Microbiology , Anti-Bacterial Agents , Therapeutic Uses , Anti-Inflammatory Agents , Therapeutic Uses , Bacteroidaceae Infections , Microbiology , Bone Density Conservation Agents , Therapeutic Uses , Cathepsin K , Interleukin-1beta , Interleukin-6 , Interleukin-8 , Isoenzymes , Macrophage Colony-Stimulating Factor , Matrix Metalloproteinase 9 , Osteoclasts , Periodontitis , Microbiology , Porphyromonas gingivalis , RANK Ligand , Rats, Sprague-Dawley , Sodium Fluoride , Therapeutic Uses , Tartrate-Resistant Acid Phosphatase , Transcription Factors , X-Ray Microtomography , MethodsABSTRACT
OBJECTIVE: This open-label study examined the effects of ramelteon on cognitive functions in 10 outpatients with schizophrenia. METHODS: Ramelteon (8 mg/day) was administered to 10 patients with schizophrenia for six months. The verbal fluency test, Trail-Making Test, the Wisconsin Card Sorting Test, the Stroop Test, the Digit Span Distraction Test, Iowa Gambling Task, the Rey Auditory Verbal Learning Test were evaluated at baseline and 6 months after treatment with ramelteon. RESULTS: Ramelteon improved significantly the scores of Rey Auditory Verbal Learning Test. Additionally, ramelteon exerted improvements in the verbal fluency and Iowa Gambling Task in 4 patients. CONCLUSION: Ramelteon could be a potential therapeutic drug, in adjunctive treatment of learning and memory deficits seen in patients with schizophrenia.