Molecular Mechanisms Controlling Bone Formation During Fracture Healing and Distraction Osteogenesis

Fracture healing and distraction osteogenesis have important applications in orthopedic, maxillofacial, and periodontal treatment. In this review, the cellular and molecular mechanisms that regulate fracture repair are contrasted with bone regeneration that occurs during distraction osteogenesis. While both processes have many common features, unique differences are observed in the temporal appearance and expression of specific molecular factors that regulate each. The relative importance of inflammatory cytokines in normal and diabetic healing, the transforming growth factor beta superfamily of bone morphogenetic mediators, and the process of angiogenesis are discussed as they relate to bone repair. A complete summary of biological activities and functions of various bioactive factors may be found at COPE (Cytokines & Cells Online Pathfinder Encyclopedia), http://www.copewithcytokines.de/cope.cgi

Proteolysis of histatins in glandular secretions and whole saliva

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (D.Sc.)--Boston University, Henry M. Goldman School of Dental Medicine, 2004 (Oral Biology).Includes bibliographical references (leaves 102-118).Histatins are a family of small, cationic, histidine-rich proteins present in human salivary secretions (Oppenheim et al., 1988). The major ones are histatin 1 (38 amino acids), histatin 3 (32 amino acids) and histatin 5 (24 amino acids), which constitute 80% of total histatins in saliva. So far only two genes for histatins have been identified, the HIS 1 gene, encoding histatin 1 and the HIS 2 gene encoding histatin 3 (Sabatini and Azen, 1989). No gene for histatin 5 has been found despite the fact that its concentration in parotid secretion (PS) and submandibular/sublingual (SMSL) secretion is comparable to that of histatin 1 and 3. In order to establish or predict histatin function in the oral cavity, it is important to know their concentrations in the various salivary secretions. Therefore, the first objective of this study is to isolate and quantify the major histatins in parotid secretion, submandibular/sublingual secretion, and in whole saliva. The recently developed zinc precipitation method was used (Flora et al., 2001) to obtain a fraction selectively enriched in histatins. The major histatins were subsequently separated by reversed-phase chromatographic procedures, and histatin concentrations were determined by comparison to standard curves for each of the histatins. The concentrations of the total major histatins in PS, SMSL and whole saliva supernatant (CHWS) from four individuals were found to range between 4.6 to 5.6 mg% in PS and from 9.8 to 18.4 mg% in SM/SL but only from 0.2 to 0.6 mg% in CHWS. Histatin levels were also compared in PS from a group of healthy individuals and periodontitis patients. The major histatin levels were higher in periodontitis patients than in healthy individuals but the differences were not statically significant due to large inter-individual variations within one group. Notably, the concentrations of histatins in CHWS were much lower than the levels in pure glandular secretions. The second objective of this study was to investigate the reason for this. It was investigated whether histatins in whole saliva were bound to bacteria and cells rather than being present in a free form, the efficiency of the zinc precipitation method in CHWS was evaluated, and the susceptibility of histatins to proteolysis in CHWS was established. It can be concluded from our observations that histatins are removed from the solute phase of saliva by over 50% upon centrifugation, that with the zinc precipitation method, 86% of the histatins remaining in the solute phase can be precipitated and that histatins are quickly degraded by proteolytic enzymes in CHWS. All three factors likely contribute to the low histatin levels observed in CHWS. The proteolytic degradation of histatins in CHWS was investigated in more detail by adding individual histatins to CHWS and by mixing PS or SMSL secretion with CHWS. To determine the primary cleavage sites in histatins, the histatin degradation patterns generated by CHWS were compared to degradation patterns generated by pure proteolytic enzymes that are known to be present in whole saliva. In particular histatin 3 and 5 added to CHWS were quickly degraded, and the major enzymes responsible for this appear to be trypsin and chymotrypsin. Interestingly histatin 1 was much more resistant to proteolysis than histatin 3 and 5. Also in this study, the stability of native histatins in PS, SMSL and CHWS was investigated. In these experiments, PS, SMSL and CHWS samples were incubated individually for a 0-120 hr time interval at 37°C. At various time intervals, aliquots were removed, boiled and analyzed by cationic PAGE. Histatin 3 in both PS and SMSL started to disappear after an hour and was completely abolished after six hours of incubation. On the other hand, histatin 1 remained stable in both glandular secretions over the entire 120 hr incubation period. It can be concluded that PS and SM/SL secretion possess minor auto-proteolytic activities which are capable of degrading histatin 3 and 5 but not histatin 1. The high resistance of native histatin 1 was an observation of interest. Since the amino acid sequences are very similar, the number of predicted proteolytic degradation sites in histatin 1 and 3 are virtually identical. It was investigated whether the proteolytic resistance of histatin 1 could be attributed to the phosphate group that is covalently linked to the amino acid serine at position 2 in histatin 1, but not in histatin 3. For this purpose, native, phosphorylated, histatin 1 and recombinant, non-phosphorylated, histatin 1 were incubated with CHWS and the proteolytic breakdown products were analyzed by cationic PAGE. Interestingly, while recombinant non-phosphorylated histatin 1 disappeared, native phosphorylated histatin 1 showed only minor losses. This result indicates that the presence of a phosphate group in position 2 in the 38 amino acid polypeptide structure of histatin 1 essentially protects this protein against proteolytic degradation

A comparative study of bovine bone used alone and in combination with transforming growth factor-beta for the treatment of periodontal osseous defects in humans

Objectives: Transforming growth factor-betas (TGFβs) are multifunctional growth factors with a broad range of biological activities in various cell types in many different tissues. The purpose of this study was to evaluate the treatment of intrabony defects with anorganic bovine bone mineral matrix combined with TGFβ-1 with the use of anorganic bovine bone alone. Materials and Methods: Thirty-two sites from sixteen patients were selected using a split-mouth study design for each patient, determined randomly through a biased coin randomization. One site received a mucoperiosteal flap, and the osseous defect was filled with the combined therapy (Group 1). The other site treated was with anorganic bovine bone alone and served as a control (Group 2). All the treated sites were covered with a bioabsorbable collagen membrane. The clinical parameters and radiographic follow-up examinations were recorded after 3, 6, 9, and 12 months. Results: Clinically, there was a statistically significant gain in the clinical attachment level (+5.03 ΁ 0.14 mm) and a statistically significant reduction of pocket probing depth (−5.16 mm ΁ 0.13) for Group 1 sites compared to sites in Group 2 (P ≤ 0.01). In addition, there were significant differences in bone density and a significant decrease of marginal bone loss after the combined therapy compared with the use of anorganic bovine bone alone (P ≤ 0.01). Conclusion: The use of anorganic bovine bone mineral matrix combined with TGFβ-1 seemed to be effective in the treatment of intrabony defects. This showed an improvement in the clinical outcome of periodontal therapy superior to the use of anorganic bovine bone on its own

The Effect of Er,Cr:YSGG and Diode Laser Applications on Dental Implant Surfaces Contaminated with Acinetobacter Baumannii and Pseudomonas Aeruginosa

Treatment of peri-implantitis through several implant surface decontamination techniques have been reported, however, some of them can negatively alter the implant surface or enhance more bacterial resistance. The aim of this in vitro study was to evaluate implant surface decontamination by means of Er,Cr:YSGG and diode lasers. Fifty micro-textured (MTX) dental implants were contaminated with Acinetobacter baumannii (n = 25) and with Pseudomonas aeruginosa (n = 25). All implants were then divided into five groups for the decontamination procedure. In group I (GI), decontamination was done with an Er,Cr:YSGG laser (2780 nm), while in group II (GII) decontamination was performed using photodynamic therapy (a 650 nm diode laser). In Group III (GIII) decontamination was performed with photodynamic therapy (an 808 nm diode laser), and in group IV (GIV) decontamination was performed with 0.12% chlorhexidine. Group V (GV) was the control group with no decontamination. After decontamination, colony forming units (CFU) were counted and implants were prepared for SEM analysis. A significant difference (p < 0.001) was observed for GI compared to the other groups, and also for GIV compared to both GII and GIII. The Er,Cr:YSGG laser (GI) showed the best results in decontaminating the implant surface. Chlorhexidine (GIV), proved to be better in decontaminating the implant surface than photodynamic therapy GII and diode laser GIII. No significant difference was found between group GII and GIII. The SEM analysis showed no significant change in the implant surface topography. The results of this study suggest that the Er,Cr:YSGG laser can be considered as an effective technique for reducing bacteria contamination on implant surfaces

Associations between maxillary labial frenum Morphology, Attachment, and Patient-Related clinical factors in Saudi Arabian Adults: Cross-sectional study

Objective: This study investigated the prevalence of maxillary labial frenum morphologies and attachment types and their associations with various patient-related clinical variables in a population of Saudi Arabian adults. Methods: This study comprehensively examined 100 participants of both genders to categorize frenum types and attachment sites. The following clinical variables were recorded: probing depth, clinical attachment loss, attached gingiva width, overjet, overbite, diastema width, central incisor condition, occlusion, previous orthodontic treatment, and the incidence of gummy smile. Results: The mean age was 32.6 years, and the average diastema width was 0.23 mm. The study found that the simple frenum type was the most common morphology (57 %), and gingival attachment was the most frequent attachment type (54 %). Simple frenum was significantly associated with class I occlusion (p = 0.018), and frenum with nichum was significantly associated with class II occlusion (p = 0.019). Females were more likely to exhibit simple frenum with nodule frenum than males (p = 0.042). Mucosal frenum attachment was significantly correlated with the absence of previous orthodontic treatment (p = 0.042). Conclusion: The study identified a relationship between the features of the maxillary labial frenum and occlusion as well as previous orthodontic treatment. Our findings suggest that understanding each patient’s unique frenum features can lead to more effective and personalized dental care, thus improving patient satisfaction