The effect of type 1 diabetes on bone healing and bone formation in standardized craniotomy defects created in BALB/cByJ mice was determined. The hypothesis that advanced glycation end products (AGEs) contribute to diminished bone healing in diabetes was evaluated by assessing for the presence of the receptor for advanced glycation end products (RAGE) by immunohistochemistry in healing craniotomy defects in diabetic animals. The effect of local application of a known RAGE protein ligand, N ⑀ -(carboxymethyl)lysine (CML)؊mouse serum albumin (MSA), on craniotomy defect healing in normal animals was then assessed and compared to the effects of control MSA. Finally, evidence in support of the expression of RAGE mRNA and protein in osteoblastic cells was obtained. The results indicated that craniotomy defects in diabetic animals healed ϳ40% of the degree to which they healed in nondiabetic animals (P < 0.05). RAGE was expressed at higher levels in healing bone tissues in diabetic compared to control animals. Further studies in nondiabetic animals indicated that bone healing was reduced by 63 and 42% in lesions treated with 900 and 90 g CML-MSA, respectively, compared to in animals treated with MSA alone (P < 0.05). Evidence for the expression of RAGE was obtained in mouse and rat osteoblastic cultures. These results support the contribution of AGEs to diminished bone healing in type 1 diabetes, possibly mediated by RAGE. Diabetes
Differentiation of phenotypically normal osteoblast cultures leads to formation of a bone-like extracellular matrix in vitro. Maximum collagen synthesis occurs early in the life of these cultures, whereas insoluble collagen deposition occurs later and is accompanied by a diminished rate of collagen synthesis. The mechanisms that control collagen deposition seem likely to include regulation of extracellular collagen biosynthetic enzymes, but expression patterns of these enzymes in differentiating osteoblasts has received little attention. The present study determined the regulation of lysyl oxidase as a function of differentiation of phenotypically normal murine MC3T3-E1 cells at the level of RNA and protein expression and enzyme activity. In addition, the regulation of BMP-1/mTLD mRNA levels that encodes procollagen C-proteinases was assayed. The role of lysyl oxidase in controlling insoluble collagen accumulation was further investigated in inhibition studies utilizing beta-aminopropionitrile, a specific inhibitor of lysyl oxidase enzyme activity. Results indicate that lysyl oxidase is regulated as a function of differentiation of MC3T3-E1 cells, and that the maximum increase in lysyl oxidase activity precedes the most efficient phase of insoluble collagen accumulation. By contrast BMP-1/mTLD is more constitutively expressed. Inhibition of lysyl oxidase in these cultures increases the accumulation of abnormal collagen fibrils, as determined by solubility studies and by electron microscopy. Taken together, these data support that regulation of lysyl oxidase activity plays a key role in the control of collagen deposition by osteoblast cultures.
The role of matrix metalloproteinases (MMPs) in the breakdown of pulp tissue of teeth with severe caries has not yet been directly elucidated. This study was to determine the levels of selected MMPs and the overall gelatinolytic activity in clinically healthy and inflamed human dental pulps of 29 healthy subjects, aged 10-19 yr. Seventeen pulps were collected from subjects diagnosed with symptomatic pulpitis, and 18 control pulps were obtained from 12 subjects following premolar extraction for orthodontic reasons. The levels of MMP-1, MMP-2, MMP-3 and MMP-9 were determined with enzyme-linked immunosorbent assay. Densitometric analysis of gelatin zymograms was used to assay gelatinolytic activity in pulp supernatants. The MMP-1 levels were below the detection limit for both groups. Levels of MMP-2 and MMP-3 were significantly lower in symptomatic vs. clinically healthy pulps. In contrast, levels of MMP-9 in inflamed pulps were significantly higher than those recorded in clinically normal pulps. The overall gelatinolytic activity was elevated in inflamed pulps compared with healthy counterparts. Further, the gelatinolytic activity was positively correlated with MMP-9 levels. The data obtained suggest a key role of MMP-9 in the breakdown of inflamed human dental pulp tissue.
The stress generation in these models may affect the integrity of periodontal structures. A better understanding of the biomechanical behavior of the PDL under physiologic and traumatic loading conditions might enhance the understanding of the biologic reaction of the PDL in health and disease.
Objectives The aim of Working Group 3 was to focus on three topics that were assessed using patient‐reported outcome measures (PROMs). These topics included the following: (a) the aesthetics of tooth and implant‐supported fixed dental prostheses focusing on partially edentulous patients, (b) a comparison of fixed and removable implant‐retained prostheses for edentulous populations, and (c) immediate versus early/conventional loading of immediately placed implants in partially edentate patients. PROMs include ratings of satisfaction and oral health‐related quality of life (QHRQoL), as well as other indicators, that is, pain, general health‐related quality of life (e.g., SF‐36). Materials and methods The Consensus Conference Group 3 participants discussed the findings of the three systematic review manuscripts. Following comprehensive discussions, participants developed consensus statements and recommendations that were then discussed in larger plenary sessions. Following this, any necessary modifications were made and approved. Results Patients were very satisfied with the aesthetics of implant‐supported fixed dental prostheses and the surrounding mucosa. Implant neck design, restorative material, or use of a provisional restoration did not influence patients’ ratings. Edentulous patients highly rate both removable and fixed implant‐supported prostheses. However, they rate their ability to maintain their oral hygiene significantly higher with the removable prosthesis. Both immediate provisionalization and conventional loading receive positive patient‐reported outcomes. Conclusions Patient‐reported outcome measures should be gathered in every clinical study in which the outcomes of oral rehabilitation with dental implants are investigated. PROMs, such as patients’ satisfaction and QHRQoL, should supplement other clinical parameters in our clinical definition of success.
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