Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model.

Introduction: Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis. Methods: Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis. Results: PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface. Conclusion: Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.

Curcumin Prevents Diabetic Osteoporosis through Promoting Osteogenesis and Angiogenesis Coupling via NF-κB Signaling.

Diabetic osteoporosis (DOP) is a metabolic disease which is characterized by impaired bone microarchitecture and reduced bone mineral density resulting from hyperglycemia. Curcumin, an effective component extracted from Curcuma longa, exhibits antioxidation, regulation of bone metabolism and hypoglycemic effects. The BMSC-mediated osteogenesis and angiogenesis coupling seems to be important in bone formation and regeneration. We aimed to explore the effect of curcumin on BMSC-mediated osteogenesis-angiogenesis coupling in high glucose conditions and underlying mechanisms. Our results showed that high glucose impaired the osteogenic and proangiogenic ability of BMSCs and that curcumin pretreatment rescued the BMSC dysfunction induced by high-concentration glucose. Inhibition of the high glucose-activated NF-κB signaling pathway has been found to contribute to the protective effects of curcumin on high glucose-inhibited coupling of osteogenesis and angiogenesis in BMSCs. Furthermore, accelerated bone loss and decreased type H vessels were observed in diabetic osteoporosis mice models. However, curcumin treatment prevented bone loss and promoted vessel formation in diabetic osteoporosis mice. Based on these results, we concluded that curcumin ameliorated diabetic osteoporosis by recovering the osteogenesis and angiogenesis coupling of BMSCs in hyperglycemia, partly through inhibiting the high glucose-activated NF-κB signaling pathway.