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Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [ i.e., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated in vitro: 1) the emergence of large multinuclear tartrate-resistant acid phosphatase-positive cells, 2) pit formation, and 3) mRNA and protein expression of CD9, but not DC-STAMP, in receptor activator of NF-κB ligand (RANKL)-stimulated OC precursor cells (OCps). While anti-DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. In our mouse model, systemic administration of anti-OC-STAMP-mAb suppressed the expression of CD9 mRNA, but not DC-STAMP mRNA, in periodontal tissue, along with diminished alveolar bone loss and reduced emergence of CD9 + OCps and tartrate-resistant acid phosphatase-positive multinuclear OCs. The present study demonstrated that OC-STAMP partners CD9 to promote periodontal bone destruction by up-regulation of fusion during osteoclastogenesis, suggesting that anti-OC-STAMP-mAb may lead to the development of a novel therapeutic regimen for periodontitis.-Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, A., Mawardi, H., Albassam, A., Kayal, R. A., Al-Dharrab, A. A., Egashira, K., Wisitrasameewong, W., Yamamoto, K., Mira, A. I., Sueishi, K., Han, X., Taubman, M. A., Miyamoto, T., Kawai, T. OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

Purpose: Periodontitis is a common chronic disease globally. It is a major cause of tooth loss among adults, and recently has been suggested as a possible risk factorfor some systemic diseases such as cardiovascular disease. In Saudi Arabia, research on periodontitis prevalence, as well as its relation to systemic diseases, is lacking. The objectives of this study were: (1) to determine the prevalence of periodontitis among a sample of Saudi Dental School patients population; and (2) to examine the association between periodontitis and systemic diseases in the selected sample., Materials and Methods: Retrospective evaluations of 282 randomly selected dental records were conducted. Age, gender, nationality and medical history were abstracted from these records. Number of remaining teeth and number of teeth with more than 20% of bone loss were determined from panoramic radiographs. Descriptive statistics, t-test, chi-square and regression models were used for data analyses., Results: About 68% of the sample had radiographic alveolar bone loss; of these, 28% had a localised and 40% had a generalised form. Prevalence of systemic diseases was generally higher among individuals with the generalised form. About 21% and 13% of those with generalised periodontitis reported history of diabetes and hypertension respectively, whereas only about 2% of those with localised periodontitis reported history of these diseases., Conclusion: The findings of the present study showed a high prevalence of periodontitis in the selected sample. There is an urgent need for further studies with larger sample size to confirm these findings and to implement an effective measure to reduce periodontitis prevalence in Saudi Arabia.