In periodontitis, alveolar bone resorption is induced by excessive host immune and inflammatory response against bacterial infection. Secretory leukocyte protease inhibitor (SLPI) has antibacterial and anti-inflammatory activity in inflammatory responses. SLPI inhibits joint inflammation and bone destruction, but the function of SLPI in periodontitis is unclear. Therefore, this study investigated whether SLPI inhibits the inflammatory response and alveolar bone resorption in LPS-induced periodontitis of rats. Micro-computed tomography and histological analysis showed that SLPI inhibited alveolar bone resorption by LPS-induced periodontitis. Immunohistochemistry revealed that SLPI decreased tumor necrosis factor-α (TNFα) and interleukine-1β (IL-1β) expression in periodontitis tissue, and decreased mRNA and protein expression of TNF-α and IL-1β in LPS-stimulated MC3T3-E1 cells. The results indicated that SLPI reduced alveolar bone resorption in LPS-induced periodontitis and inhibited inflammatory cytokine, such as TNF-α and IL-1β, expression in LPS-stimulated MC3T3-E1 preosteoblasts. Therefore, SLPI could be a regulatory molecule by inhibiting alveolar bone resorption through the reduction of inflammatory cytokines, and inducing osteoblast activation for bone formation. ARTICLE HISTORY

Thymosin β4 (Tβ4) is known to inhibit an inflammatory response and to increase the survival of osteoblasts on titanium (Ti) surfaces. Ti is the most widely used graft material in dentistry; however, an inflammatory response induced following implant placement results in the generation of reactive oxygen species (ROS). The oxidative stress from the production of ROS such as nitric oxide (NO) and hydrogen peroxide (H2O2) can damage surrounding cells, resulting in implant failure by decreasing cell viability. Thus, the aim of this study was to determine the biological effects of Tβ4 on the oxidative stress induced to MC3T3-E1 preosteoblasts on the Ti surface. Based on an MTT assay and bromodeoxyuridine immunofluorescence staining, Tβ4 was found to increase the proliferation of the H2O2-exposed MC3T3-E1 cells on Ti discs. Reverse transcription-polymerase chain reaction and western blot analyses showed that Tβ4 decreased the mRNA and protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in H2O2-exposed MC3T3-E1 cells on the Ti discs. Tβ4 inhibited the synthesis of intracellular ROS and the secretion of NO and prostaglandin E2 (PGE2) from H2O2-exposed MC3T3-E1 cells on the Ti discs. In conclusion, Tβ4 inhibits H2O2-induced iNOS and COX-2 expression with a decrease in ROS, NO, and PGE2 synthesis, which leads to improved cell survival with low cytotoxicity under an oxidative stress condition in MC3T3-E1 cells on the Ti surface. This suggests that Tβ4 may be a crucial molecule to reduce oxidative stress-induced cell damage or hypoxia, leading to promoted osseointegration on the Ti surface during implant placement.

Thymosin β4 (Tβ4) has been recently reported to play a role in dentinogenesis by regulating the expression of dentin matrix proteins. Based on previous studies, it is hypothesized that Tβ4 is associated with the formation of the enamel matrix and thus plays an important role in ameloblast. However, there is no report on the function of Tβ4 during tooth development so far. Therefore, in this study, we aimed to investigate the expression of Tβ4 and its function in ameloblasts during mouse tooth development. Tβ4 was expressed strongly in the tooth bud at the bud stage and in the dental lamina and oral epithelium at the cap stage. In advanced bell stage at postnatal day 4, large elongated ameloblasts were observed and the expression of the Tβ4 protein was the highest, with the enamel being was thicker than that in the early bell stage. The length of ameloblasts increased from the presecretory to the secretory stage and decreased from the maturation to the protective stage. These results suggest that Tβ4 participates not only in the proliferation of oral epithelial cells during the early stage of tooth development but also regulates enamel protein secretion in ameloblasts and enamel mineralization.