Progression of periodontal destruction and the roles of advanced glycation end products in experimental diabetes.

BACKGROUND: Progression of diabetes-associated periodontal destruction and the roles of advanced glycation end products (AGEs) are investigated. METHODS: Diabetes was induced by streptozocotin injection, and periodontitis was induced via silk ligature placement with Porphyromonas gingivalis lipopolysaccharide injection in 64 Sprague-Dawley rats for 7 to 21 days. The quality of alveolar bone and attachment loss (AL) were measured by microcomputed tomography and histology. Destruction profiles were evaluated by histology, histochemistry, immunohistochemistry, and quantitative assessments of inflammatory cells, expression of receptors for AGEs (RAGE), tartrate-resistant acid phosphatase, and proliferating cell nuclear antigen. RESULTS: Without periodontitis induction, there was no obvious morphologic change in the periodontium, although slight elevations of AGEs and RAGE levels were noted in animals with diabetes. In the group with experimental periodontitis, significant periodontal bone loss was noted in animals both with and without diabetes from day 7, with more progressive bone loss in animals with diabetes during days 14 to 21. Histologically, the disruption of attachment and inflammation were observed from day 7, but subsequently subsided in animals without diabetes. A stronger and more prolonged response with significant AL was observed in animals with diabetes. Stronger inflammation, attenuated and persistent resorptive activity, and weaker proliferating potential were demonstrated by animals with diabetes. AGE deposition and RAGE expression were noted in animals without diabetes but with periodontitis, although levels were considerably elevated in the later stages in animals with diabetes. CONCLUSIONS: Diabetes augments periodontal destruction by reducing the proliferating capability and activating resorptive activities. Presence of the AGE-RAGE axis without diabetes implies that it is involved in the regulation of inflammation.

Biocompatibility of PDGF-simvastatin double-walled PLGA (PDLLA) microspheres for dentoalveolar regeneration: a preliminary study.

Proper coordination of local signal to harmonize mitogenesis and osteogenic differentiation is one of the prerequisites to optimize dentoalveolar regeneration. In the study, we purpose to fabricate controlled-release microspheres encapsulating platelet-derived growth factor (PDGF) and simvastatin by coaxial electrohydrodynamic atomization. The microspheres demonstrated a distinct core and shell structure encapsulating PDGF and simvastatin respectively, and the encapsulation efficiency was 82.45-92.16% in-core and 51.37-71.34% in-shell. Sequential release of PDGF and simvastatin was seen in simvastatin-in-core and PDGF-in-shell (SP) design, and simultaneous release was achieved in PDGF-in-core and simvastatin-in-shell (PS) design. All microspheres demonstrated acceptable biocompatibility in vivo, with increased proliferation, reduced apoptosis, and reduced inflammation while PDGF or simvastatin was encapsulated. The PS design significantly reduced apoptosis than control, whereby significant and persistent enhanced proliferation was noted in SP group. The thickness of fibrotic capsules surrounding microspheres significantly reduced in both SP and PS group at day 14. The finding demonstrates that synergism of PDGF and simvastatin favored biocompatibility. Further investigations will aim on confirming the regenerative effect of SP and PS microspheres in a more clinically relevant model.

The effects of acellular amniotic membrane matrix on osteogenic differentiation and ERK1/2 signaling in human dental apical papilla cells.

The amniotic membrane (AM) has been widely used in the field of tissue engineering because of the favorable biological properties for scaffolding material. However, little is known about the effects of an acellular AM matrix on the osteogenic differentiation of mesenchymal stem cells. In this study, it was found that both basement membrane side and collagenous stroma side of the acellular AM matrix were capable of providing a preferential environment for driving the osteogenic differentiation of human dental apical papilla cells (APCs) with proven stem cell characteristics. Acellular AM matrix potentiated the induction effect of osteogenic supplements (OS) such as ascorbic acid, ß-glycerophosphate, and dexamethasone and enhanced the osteogenic differentiation of APCs, as seen by increased core-binding factor alpha 1 (Cbfa-1) phosphorylation, alkaline phosphatase activity, mRNA expression of osteogenic marker genes, and mineralized matrix deposition. Even in the absence of soluble OS, acellular AM matrix also could exert the substrate-induced effect on initiating APCs' differentiation. Especially, the collagenous stroma side was more effective than the basement membrane side. Moreover, the AM-induced effect was significantly inhibited by U0126, an inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) signaling. Taken together, the osteogenic differentiation promoting effect on APCs is AM-specific, which provides potential applications of acellular AM matrix in bone/tooth tissue engineering.

Patterns of diabetic periodontal wound repair: a study using micro-computed tomography and immunohistochemistry.

BACKGROUND: Diabetes is known to impair wound healing and deteriorate the periodontal condition. There is limited information about the patterns and events associated with periodontal wound repair. In this study, we evaluate the dynamics of periodontal wound repair using micro-computed tomography (microCT) and immunohistochemistry. METHODS: Thirty-six male rats were used, and diabetes was induced by streptozotocin. The maxillary first molars were extracted, and a tooth-associated osseous defect was created in the extraction area. Animals were sacrificed after 7, 14, and 21 days. Volumetry and distribution of bone trabeculae were evaluated by microCT imaging. The patterns of healing and collagen alignment were evaluated by histology. Advanced glycation end-product (AGE) deposition and expression of the receptor for AGEs (RAGE), tartrate-resistant acid phosphatase, and proliferating cell nuclear antigen were evaluated by histochemical and immunohistochemical staining. RESULTS: Diabetic animals demonstrated a significantly reduced bone volume and trabecular number as well as thinner trabeculae and more trabecular separation in osseous defects. The early stage was characterized by significantly reduced cellular proliferation and prolonged active inflammation without evident bone resorption, whereas delayed recovery of collagen realignment, matrix deposition, and bone turnover was noted in later stages. Although AGEs and RAGE were present during healing in diabetes and controls, a stronger and more persistent level of expression was observed in the group with diabetes CONCLUSIONS: Diabetes significantly delayed osseous defect healing by augmenting inflammation, impairing proliferation, and delaying bone resorption. The AGE-RAGE axis can be activated under metabolic disturbance and inflammation.