Pyrroloquinoline quinone plays an important role in rescuing Bmi-1-/- mice induced developmental disorders of teeth and mandible--anti-oxidant effect of pyrroloquinoline quinone

Am J Transl Res. 2018 Jan 15;10(1):40-53. eCollection 2018.

Abstract

To investigate whether pyrroloquinoline quinine (PQQ) plays an important role in rescuing Bmi-1-/- mice induced developmental disorders of teeth and mandible by regulating oxidative stress. We fed Bmi-1-/- mice a diet supplemented with PQQ (BKO+PQQ), BKO mice with normal diet (BKO) and wild type mice with normal diet (WT) as controls. We compared the differences of dental, mandibular phenotype by means of X-ray photography, micro CT scanning and three-dimensional reconstruction, HE staining, histochemistry, immunoistohemistry, TUNEL staining, Western blot and Flow cytometry in three groups of animals. Results showed that BKO+PQQ mice increased morphology of teeth and mandible, decreased X-ray transmittance, and increased bone density compared with BKO mice. Results also showed that the teeth volume and the dentin sialoprotein (DSP) immunopositive areas, the cortical thickness, alveolar bone volume, osteoblast number and activity, and alkaline phosphatase (ALP), Osteocalcin (OCN) and type I collagen (Col 1) were all reduced significantly in BKO mice compared with their wild-type littermates, whereas these parameters were increased significantly in BKO+PQQ mice compared with BKO mice. Our study indicated that, compared BKO mice, PCNA positive cells percentage of mandibular first molar epithelial root sheath area significantly increased in BKO+PQQ mice, and TUNEL positive cells percentage was significantly decreased. Further studies showed that supplemental PQQ played a role in anti-osteoporosis of teeth and mandible by up-regulating anti-oxidant capacity, inhibiting oxidative stress and reducing DNA damage, down-regulating CDKI proteins levels, and decreasing cell apoptosis. This study demonstrated that PQQ played an important role in rescuing mandible osteoporosis and disorder of teeth development in BKO mice by promoting osteoblastic bone formation of mandibular alveolar bone, inhibiting osteoclastic bone resorption, promoting odontoblast cell proliferation of epithelial root sheath area, inhibiting cell apoptosis, scavenging ROS.

Keywords: Bmi-1; Pyrroloquinoline quinone; mandible; oxidative stress; teeth.