Maria Ransjö

Soluble silica inhibits osteoclast formation and bone resorption in vitro

Several studies have suggested that silicon (Si) may be essential for the normal development of connective tissue and the skeleton. Positive effects of Si from the diet as well as from Si-containing biomaterials, such as bioactive glass 45S5 (BG), have been demonstrated. Studies have reported that Si stimulates osteoblast proliferation and differentiation. However, the effects of Si on osteoclasts have not been directly addressed. The purpose of the present in vitro study was to clarify if Si has regulatory effects on osteoclast formation and bone resorption. The effects of BG, BG dissolution extracts and Si containing cell culture medium were investigated in a mouse calvarial bone resorption assay and osteoclast formation assays (mouse bone marrow cultures and RAW264.7 cell cultures). We conclude from our results that Si causes significant inhibition of osteoclast phenotypic gene expressions, osteoclast formation and bone resorption in vitro. In conclusion, the present study suggests that Si has a dual nature in bone metabolism with stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. This suggested property of Si might be interesting to further explore in future biomaterials for treatments of bone defects in patients.

In vitro study of the biological interface of Bio‐Oss: implications of the experimental setup

OBJECTIVESnTo systematically investigate the biological interface of Bio-Oss by analysing dissolution-precipitation behaviour and osteogenic responses using in vitro experimental systems.nnnMATERIAL AND METHODSnDifferent concentrations (1-100xa0mg/ml) of Bio-Oss were incubated in cell culture medium for 24xa0h before elemental concentrations for calcium, phosphorus and silicon in the medium were analysed with inductive coupled plasma-optical emission spectroscopy. Radioactive calcium-45 isotope labelling technique was used to study possible precipitation of calcium on the Bio-Oss particle. Biological interface of Bio-Oss was studied in osteogenic experiments using mineralization medium and three different sources of cells (primary mouse bone marrow stromal cells, primary rat calvarial cells and MC3T3-E1 mouse pre-osteoblast cell line). Cells were fixed and stained with Toulidine blue, von Kossa or Alizarin Red staining for confirmation of extracellular matrix mineralization.nnnRESULTSnElemental analysis of the cell culture medium demonstrated a significant decrease of calcium and phosphorus and a dose-dependent release of silicon to the medium after incubation with Bio-Oss. A significant decrease of calcium and phosphorus in the medium occurred even at low concentrations of Bio-Oss. Uptake of calcium on the Bio-Oss particle was confirmed with radioactive calcium-45 isotope labelling technique. In osteogenic experiments with Bio-Oss (<1xa0mg/ml), matrix mineralization around the Bio-Oss particles were demonstrated in all three cell types with von Kossa and Alizarin Red staining.nnnCONCLUSIONnDissolution-precipitation reactions occur at the surface of Bio-Oss, and osteogenic responses are seen at the biological interface. The concentration of Bio-Oss is a key factor for the experimental in vitro results, and may also have implications for the clinic.

Digital casts in orthodontics: A comparison of 4 software systems

INTRODUCTIONnThe introduction of digital cast models is inevitable in the otherwise digitized everyday life of orthodontics. The introduction of this new technology, however, is not straightforward, and selecting an appropriate system can be difficult. The aim of the study was to compare 4 orthodontic digital software systems regarding service, features, and usability.nnnMETHODSnInformation regarding service offered by the companies was obtained from questionnaires and Web sites. The features of each software system were collected by exploring the user manuals and the software programs. Replicas of pretreatment casts were sent to Cadent (OrthoCAD; Cadent, Carlstadt, NJ), OthoLab (O3DM; OrthoLab, Poznan, Poland), OrthoProof (DigiModel; OrthoProof, Nieuwegein, The Netherlands), and 3Shape (OrthoAnalyzer; 3Shape, Copenhagen, Denmark). The usability of the programs was assessed by experts in interaction design and usability using the enhanced cognitive walkthrough method: 4 tasks were defined and performed by a group of domain experts while they were observed by usability experts.nnnRESULTSnThe services provided by the companies were similar. Regarding the features, all 4 systems were able to perform basic measurements; however, not all provided the peer assessment rating index or the American Board of Orthodontics analysis, simulation of the treatment with braces, or digital articulation of the casts. All systems demonstrated weaknesses in usability. However, OrthoCAD and 03DM were considered to be easier to learn for first-time users.nnnCONCLUSIONSnIn general, the usability of these programs was poor and needs to be further developed. Hands-on training supervised by the program experts is recommended for beginners.

Clinical predictors of maxillary canine impaction: a novel approach using multivariate analysis

BackgroundnEctopic eruption and/or impaction of maxillary permanent canines is a frequent problem in clinical dentistry. Previous studies aimed to identify potential associated factors and predictors for impacted maxillary canines have only used conventional univariate statistics, which does not allow the analysis of the interaction between and within variables. Multivariate data analysis (MVDA) is a better and more powerful tool for the integration and interpretation of complex datasets.nnnAimnThe aim of this study was to validate previously explored predictors of permanent maxillary canine impaction using MVDA.nnnSubjects and methodsnThis cohort study included all the patients referred during 2011 to Mölndal Hospital, Sweden for surgical exposure of impacted canines (N = 45). Age- and gender-matched orthodontic patients (N = 45) with normally erupting canines comprised the control group. The age range for both groups was 11-17 years. The positions of the canine teeth (orthopantograms), the skeletal variables (profile radiographs), and dentoalveolar traits (casts) were evaluated as potential predictive factors for impaction.nnnResultsnNone of the parameters evaluated with either profile radiography or casts were positively correlated with impacted maxillary canines, with the exception of the location of the already impacted canines, as identified by orthopantogram.nnnConclusionnNo correlation between clinical variables and impaction was found using MVDA. Therefore, these variables could not be used as predictors of canine impaction. Other types of parameters, such as inheritance and molecular factors that regulate the biological mechanisms of the eruption process, need to be further investigated.

Stability and Side Effects of Orthodontic Retainers - A Systematic Review

Background: The role of orthodontic retainers in maintaining stability after orthodontic treatment, and side effects associated with orthodontic retainers have not been well established. nObjective: To investigate whether fixed retainers improve stability after orthodontic treatment, or increase the risk of side effects on the teeth and periodontium in comparison with removable retainers, no retainer, or fiberotomy. nMethods: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, HTAdatabases of NHS Centre for Reviews and Dissemination, Swedish Council on Health Technology Assessment (SBU), Norwegian Knowledge Centre for the Health Services (NOKC), Danish Health and Medicines Authority, and reference lists. Data extraction was verified by at least two authors. The quality of evidence was rated. Meta-analysis was not suitable. nResults: Two systematic reviews (SR), two randomized controlled trials (RCT), four non-randomized controlled studies (CT), and five case series were included. The SRs were well reported, but addressed issues that differed from the addressed question, or did not add to the identified primary studies. Both RCTs and CTs had study limitations, and problems with directness and/or precision. None of the studies compared fixed retainers to fiberotomy. nConclusion: According to the literature there is only low quality of evidence, that treatment stability may be improved by a fixed retainer after orthodontic treatment in comparison with a removable retainer, or no retainer (GRADE ⊕⊕âx83x9dâx83x9d). Furthermore, there is very low quality of evidence, whether periodontal outcomes, dental caries prevalence, or presence of calculus differ between the various types of retainer regimens (GRADE ⊕âx83x9dâx83x9dâx83x9d).

What Factors Are Associated With Impacted Canines in Cleft Patients

PURPOSEnIt is important to predict and prevent the impaction of canines. The aim of this study was to estimate the prevalence of impacted canines in patients with unilateral cleft lip and palate (UCLP) and to identify factors associated with impaction.nnnMATERIALS AND METHODSnThis retrospective cohort study included patients with nonsyndromic UCLP. The predictors were pre-eruptive inclination angle, deviation in tooth number (agenesis or supernumerary lateral incisors), and reoperation of bone transplant. The outcome variable was impacted and surgically exposed canines.nnnRESULTSnThe prevalence of impacted and surgically exposed canines in the 68 consecutive patients with UCLP was 20.6%. The pre-eruptive inclination angle was significantly larger (34.4°) for the impacted canines on the cleft side compared with the spontaneously erupted canines on the cleft and non-cleft sides (25.5° vs 15.4; P < .05). Reoperation of the bone transplant significantly increased canine impaction (50%; P < .05).nnnCONCLUSIONnThe eruption of maxillary canines needs to be supervised carefully in patients with UCLP, because the prevalence of impaction is 10 times higher compared with the general population. Factors associated with canine impaction are a pre-eruptive inclination larger than 30° and reoperation of the bone transplant.

Effects of Porphyromonas gingivalis surface-associated material on osteoclast formation

Porphyromonas gingivalis strongly correlates with periodontitis, but the underlying mechanisms causing dentoalveolar bone resorption are not fully understood. As contradictory effects of P. gingivalis on osteoclastogenesis have been reported, this study investigates the effect of P. gingivalis extract on osteoclast formation. Osteoclast formation in mouse bone marrow (MBM) cell cultures and RAW 264.7 cells was stimulated by nuclear factor-κB ligand (RANKL) or parathyroid hormone (PTH). Cells were cultured with and without P. gingivalis surface-associated material and phenotypic characteristics were examined using microscopy, flow cytometry, and RT-PCR. P. gingivalis significantly decreased osteoclast formation and the expression of osteoclast phenotypic markers in PTH-stimulated MBM cultures. Additionally, P. gingivalis inhibited expression of osteoclast differentiation factors and stimulated expression of the mouse macrophage marker F4/80. The presence of P. gingivalis in RANKL-stimulated MBM cultures and RAW 264.7 cells inhibited osteoclastogenesis. Interestingly, a transient exposure with P. gingivalis before PTH stimulation increased osteoclastogenesis in MBM cultures. Flow cytometric analyses of cells transiently exposed to P. gingivalis demonstrated an increased proportion of potential osteoclast precursor cells. We conclude that a transient exposure of MBM cultures to P. gingivalis increases the number of osteoclast precursors and osteoclast formation, whereas a prolonged exposure completely abolishes osteoclastogenesis.

Cone-beam computed tomographic evaluation of the long-term effects of orthodontic retainers on marginal bone levels

Introduction Fixed retainers are widely used after orthodontic treatment, sometimes for extended periods, despite insufficient knowledge of their possible long‐term adverse effects on the periodontium. The aim of this study was to evaluate whether bonded orthodontic retainers have an adverse long‐term effect on the marginal bone levels of the mandibular front teeth. Methods The study included 62 consecutive patients in 3 groups: (1) patients who underwent orthodontic treatment and wore a fixed retainer for 10 years, (2) patients who underwent orthodontic treatment but did not have a fixed retainer, and (3) untreated controls. The marginal bone levels were measured by cone‐beam computed tomography 10 years after treatment. Additionally, multivariate data analysis was used to analyze possible correlations between the marginal bone levels at 10 years and the variables obtained from the study casts and profile radiographs. Results The results demonstrated a significantly lower marginal bone level on the buccal side of the mandibular front teeth in the orthodontically treated patients compared with the orthodontically untreated group. There was no difference in the marginal bone levels between the retainer group and the no‐retainer group. Multivariate analysis indicated that a low marginal bone level was correlated with a basal open vertical relationship, posterior rotation of the mandible, pretreatment of the incisor protrusion, and extraction therapy. Conclusions Within the limits of this research design, the long‐term retention phase in general does not seem to cause any adverse effects on the marginal bone levels after 10 years. HighlightsLong‐term bonded lingual retention does not adversely affect marginal bone level.Orthodontic patients had lower marginal bone levels buccally on the mandibular front teeth.Low marginal bone level was correlated with a basal open vertical relationship.It was also correlated with mandibular posterior rotation in orthodontic patients.

Insulin released from titanium discs with insulin coatings—Kinetics and biological activity

Local administration of insulin from a titanium surface has been demonstrated to increase bone formation in non-diabetic rats. The authors hypothesized that insulin was released from the titanium surface and with preserved biological activity after the release. Thus, in the present in vitro study, human recombinant insulin was immobilized onto titanium discs, and the insulin release kinetics was evaluated using Electro-chemiluminescence immunoassay. Neutral Red uptake assay and mineralization assay were used to evaluate the biological effects of the released insulin on human osteoblast-like MG-63 cells. The results confirmed that insulin was released from titanium surfaces during a six-week period. Etching the disc prior to insulin coating, thickening of the insulin coating and incubation of the discs in serum-enriched cell culture medium increased the release. However, longer storage time decreased the release of insulin. Furthermore, the released insulin had retained its biological activity, as demonstrated by the significant increase in cell number and a stimulated mineralization process, upon exposure to released insulin.

Gene expression profiles in dental follicles from patients with impacted canines

Animal studies suggest that the dental follicle (DF) plays a major role in tooth eruption. However, the role of the DF during tooth impaction and related root resorptions in adjacent teeth is not clear. The hypothesis for the present study is that expression of regulatory factors involved in the bone remodelling process necessary for tooth eruption may differ between dental follicles from teeth with different clinical situations. We have analysed the gene expression profiles in the DF obtained from impacted canines, with (Nxa0=xa03) or without (Nxa0=xa05) signs of root resorption, and from control teeth (normal erupting teeth, mesiodens) (Nxa0=xa03). DF from 11 patients (mean age: 13xa0years) obtains at the time of surgical exposure of the tooth. Due to the surgical time point, all teeth were in a late developmental stage. Gene expression related to osteoblast activation/bone formation, osteoclast recruitment and activation was analysed by RTqPCR. Genes related to bone formation (RUNX2, OSX, ALP, OCN, CX43) were highly expressed in all the samples, but osteoclast recruitment/activation markers (OPG, RANKL, MCP-1, CSF-1) were negligible. No apparent patterns or significant differences in gene expression were found between impacted canines, with or without signs of root resorption, or when compared to control teeth. Our results suggest the DF regulation of osteoclastic activity is limited in the late pre-emergent stage of tooth development, irrespective if the tooth is normally erupting or impacted. We suggest that the follicle may have an important regulatory function for alveolar bone formation in the final eruption process and CX43-gap junction communication could be an important signalling pathway.