Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with keratinocyte-specific Foxo1 deletion. Diabetic mucosal wounds had significantly delayed healing with reduced cell migration and proliferation. Foxo1 deletion rescued the negative impact of diabetes on healing but had the opposite effect in normoglycemic mice. Diabetes in vivo and in high glucose conditions in vitro enhanced expression of chemokine (C-C motif) ligand 20 (CCL20) and interleukin-36γ (IL-36γ) in a Foxo1-dependent manner. High glucose–stimulated Foxo1 binding to CCL20 and IL-36γ promoters and CCL20 and IL-36γ significantly inhibited migration of these cells in high glucose conditions. In normal healing, Foxo1 was needed for transforming growth factor-β1 (TGF-β1) expression, and in standard glucose conditions, TGF-β1 rescued the negative effect of Foxo1 silencing on migration in vitro. We propose that Foxo1 under diabetic or high glucose conditions impairs healing by promoting high levels of CCL20 and IL-36γ expression but under normal conditions, enhances it by inducing TGF-β1. This finding provides mechanistic insight into how Foxo1 mediates the impact of diabetes on mucosal wound healing.

Type 1 diabetes impairs fracture healing. We tested the hypothesis that diabetes affects chondrocytes to impair fracture healing through a mechanism that involves the transcription factor FOXO1. Type 1 diabetes was induced by streptozotocin in mice with FOXO1 deletion in chondrocytes (Col2α1Cre+.FOXO1L/L) or littermate controls (Col2α1Cre−.FOXO1L/L) and closed femoral fractures induced. Diabetic mice had 77% less cartilage and 30% less bone than normoglycemics evaluated histologically and by micro-computed tomography. Both were reversed with lineage-specific FOXO1 ablation. Diabetic mice had a threefold increase in osteoclasts and a two- to threefold increase in RANKL mRNA or RANKL-expressing chondrocytes compared with normoglycemics. Both parameters were rescued by FOXO1 ablation in chondrocytes. Conditions present in diabetes, high glucose (HG), and increased advanced glycation end products (AGEs) stimulated FOXO1 association with the RANKL promoter in vitro, and overexpression of FOXO1 increased RANKL promoter activity in luciferase reporter assays. HG and AGE stimulated FOXO1 nuclear localization, which was reversed by insulin and inhibitors of TLR4, histone deacetylase, nitric oxide, and reactive oxygen species. The results indicate that chondrocytes play a prominent role in diabetes-impaired fracture healing and that high levels of glucose, AGEs, and tumor necrosis factor-α, which are elevated by diabetes, alter RANKL expression in chondrocytes via FOXO1.

The aim of this study is to evaluate the longitudinal transverse growth of the maxillo-mandibular complex in untreated children using the Cone Beam Computed Tomography (CBCT). Two sets of scans on 12 males (mean 8.75 years at T1 and 11.52 years at T2) and 18 females (mean 9.09 years at T1 and 10.80 years at T2) were analyzed using Dolphin 3D imaging. The transverse widths of various maxillary and mandibular skeletal landmarks and the dentoalveolar and dental landmarks at the level of first molars were measured. Overall, there were greater increases in the transverse dimension in the posterior than anterior portions of the maxilla and mandible. The increase in intergonial width of the mandible seems to be primarily due to the lengthening of the mandibular body. The dentoalveolar process at the first molar level increases at an equal rate corono-apically and is independent to the changes in molar inclination. When comparing maxillary dentoalveolar changes with that of the mandible, greater increases were noticed in the maxilla, which might be explained by the presence of sutural growth in the maxilla. Moreover, the first molars maintain their coordination with each other despite the differential increase in the maxillary and mandibular dentoalveolar processes.

The aim of this longitudinal study was to evaluate the sagittal and vertical growth of the maxillo–mandibular complex in untreated children using orthogonal lateral cephalograms compressed from cone beam computed tomography (CBCT). Two sets of scans, on 12 males (mean 8.75 years at T1, and 11.52 years at T2) and 18 females (mean 9.09 years at T1, and 10.80 years at T2), were analyzed using Dolphin 3D imaging. The displacements of the landmarks and rotations of both jaws relative to the cranial base were measured using the cranial base, and the maxillary and mandibular core lines. From T1 to T2, relative to the cranial base, the nasion, orbitale, A-point, and B-point moved anteriorly and inferiorly. The porion moved posteriorly and inferiorly. The ANB and mandibular plane angle decreased. All but one subject had forward rotation in reference to the cranial base. The maxillary and mandibular superimpositions showed no sagittal change on the A-point and B-point. The U6 and U1 erupted at 0.94 and 1.01 mm/year (males) and 0.82 and 0.95 mm/year (females), respectively. The L6 and L1 erupted at 0.66 and 0.88 mm/year (males), and at 0.41 mm/year for both the L6 and the L1 (females), respectively.

In the article cited above, the affiliation “Department of Periodontics, College of Dentistry, Taibah University, Medina, Saudi Arabia” was inadvertently omitted for author Badr Othman. The authors apologize for the error. The online version of the article (https://doi.org/10.2337/db14-0589) has been updated to correct the error.