Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed. High OPG expression was expected to have a negative regulatory effect on odontoclastogenesis; however, odontoclasts were not detected in the dental pulp of OPG-deficient (KO) mice. In contrast, damage induced odontoclast-like cells were seen in wild-type pulp tissues, with their number significantly increased in OPG-KO mice. Relative ratio of RANKL/OPG in the damaged pulp was significantly higher than in undamaged control pulp. Pulp damages enhanced hypoxia inducible factor-1α and -2α, reported to increase RANKL or decrease OPG. These results reveal that the relative ratio of RANKL/OPG is significant to pulpal odontoclastogenesis, and that OPG expression is not required for maintenance of pulp homeostasis, but protects pulp from odontoclastogenesis caused by damages.

Sclerostin is secreted from osteocytes, binds to the Wnt co-receptor Lrp5/6, and affects the interaction between Wnt ligands and Lrp5/6, which inhibits Wnt/β-catenin signals and suppresses bone formation. Sclerostin plays an important role in the preservation of bone mass by functioning as a negative regulator of bone formation. A sclerostin deficiency causes sclerosteosis, which is characterized by an excess bone mass with enhanced bone formation in humans and mice. The expression of sclerostin is positively and negatively regulated by many factors, which also govern bone metabolism. Positive and negative regulators of sclerostin expression and their effects are introduced and discussed herein based on recent and previous findings, including our research.

Background: to evaluate the association between type 2 diabetes and periodontal disease severity using the rate of alveolar bone loss (ABL) and high-sensitivity C-reactive protein (hs-CRP) value as indices. Methods: In this cross-sectional study of 372 patients (mean age ± SD, 53.2 ± 11.8 years) from a Japanese hospital, we measured ABL and number of teeth on either panoramic radiographs or intraoral dental radiographs of all teeth. Periodontal disease severity was classified into nine groups by combining ABL and hs-CRP. Results: 48 subjects had type 2 diabetes; 324 did not. Univariate analysis showed that type 2 diabetes was significantly associated with age, sex, body mass index, number of teeth, ABL, hs-CRP, and periodontal disease severity. Multivariate analysis showed significant associations between type 2 diabetes and the groups with high severity of periodontal disease. In receiver operating characteristic (ROC) curve analysis, predicting the presence of diabetes, area under the ROC curve was 0.762 (95%CI = 0.688–0.835) for ABL, and 0.709 (95%CI = 0.635–0.784) for hs-CRP, which was significant. Conclusions: this study showed that diabetes can be associated with a periodontal disease severity classification using the combination of ABL and hs-CRP.