Oxysterols, oxygenated by-products of cholesterol biosynthesis, play roles in various physiological and pathological systems. However, the effects of oxysterols on periodontal regeneration are unknown. This study investigated the effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in-vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar bone defect. To evaluate the effects of the combined oxysterols on PDLSC biology, we studied the SS-induced osteogenic differentiation of PDLSCs by assessing alkaline phosphatase activity, intracellular calcium levels [Ca2+]i, matrix mineralization, and osteogenic marker mRNA expression and protein levels. To verify the effect of oxysterols on alveolar bone regeneration, we employed tooth extraction bone defect models. Oxysterols increased the osteogenic activity of PDLSCs compared with the control group. The expression of liver X receptor (LXR) α and β, the nuclear receptors for oxysterols, and their target gene, ATP-binding cassette transporter A1 (ABCA1), increased significantly during osteogenesis. Oxysterols also increased protein levels of the hedgehog (Hh) receptor Smo and the transcription factor Gli1. We further confirmed the reciprocal reaction between the LXRs and Hh signaling. Transfection of both LXRα and LXRβ siRNAs decreased Smo and Gli1 protein levels. In contrast, the inhibition of Hh signaling attenuated the LXRα and LXRβ protein levels. Subsequently, SS-induced osteogenic activity of PDLSCs was suppressed by the inhibition of LXRs or Hh signaling. The application of SS also enhanced bone formation in the defect sites of in-vivo models, showing equivalent efficacy to recombinant human bone morphogenetic protein-2. These findings suggest that a specific combination of oxysterols promoted periodontal regeneration by regulating PDLSC activity and alveolar bone regeneration.

Maxillary sinus floor augmentation (MSFA) is widely used and considered a predictable procedure for implant placement. However, the influence of MSFA on implant survival and marginal bone loss (MBL) is still inconclusive. The purpose of this retrospective observational study is to evaluate the long-term genuine influence of MSFA on the survival and MBL of implants by comparing those with and without MSFA only in maxillary molars within the same patients. Thirty-eight patients (28 male and 10 female), with a total of 119 implants, received implants with and without MSFA, and were followed up for 5.8 to 22 years. Patient- and implant-related factors were assessed with a frailty model for implant survival and with generalized estimation equations (GEE) for MBL around the implant. No variables showed a statistical significance for implant failure in the frailty model. In GEE analysis for MBL, MSFA did not show any statistical significance. In conclusion, MSFA demonstrated no significant influence on implant failure and MBL in posterior maxilla in this study.