Biomedical subjects

Miron Weinreb

Publications and source records attributed to Miron Weinreb.

10 recordsLinked to original sources

PubMed2026

Decoding regional keratinization in human oral mucosa through high-resolution spatial transcriptomics.

Oral mucosa exhibits region-specific keratinization, essential for periodontal health, yet the spatial and molecular mechanisms driving these differences remain poorly understood. This study aimed to generate a high-resolution spatial transcriptomic atlas of the human oral mucosa around the mucogingival junction, to reveal stromal-epithelial interactions, that distinguish keratinized from non-keratinized programs. Formalin-fixed paraffin-embedded specimens from the mucogingival junction area of two healthy donors were analyzed with the 10 × Genomics Visium HD platform, yielding two keratinized and two non-keratinized regions. Spatial clustering, pseudotime trajectory inference, cell-type integration with a single-cell reference, and ligand-receptor network analysis were applied to delineate epithelial and stromal compartments. Sixteen reproducible clusters, recapitulating tissue architecture, were identified and revealed distinct transcriptional signatures, distinguishing gingiva from lining mucosa. Pseudotime analysis revealed bifurcating epithelial lineages, originating from a shared basal progenitor layer into keratinized and non-keratinized programs. Gingival keratinization was driven by stromal collagen ligands (COL1A1, COL1A2, COL6A1, COL6A2) engaging epithelial receptors (CD44, SDC1), further reinforced within the epithelium by desmosomal adhesion via DSG1-DSC2/3. Gingival keratinization emerges from integrated stromal collagen signaling and epithelial adhesion. This spatially resolved framework advances understanding of oral mucosal specialization and provides a foundation for biologically guided regenerative therapies.

Humans↗

PubMed2006

Effect of enamel matrix protein derivative on healing of surgical supra-infrabony periodontal defects in the rat molar: a histomorphometric study.

BACKGROUND: Enamel matrix protein derivative (EMD) has proven to enhance periodontal regeneration in human and animal studies. The present histomorphometric study evaluated healing of combined supra-infrabony periodontal defects with EMD. METHODS: The study comprised two groups of 10 Wistar rats each, 7 to 8 months old. Bony defects were created on the mesial aspect of the mesial root of the first maxillary molar. The root surface was planed and 24% EDTA gel applied for 2 minutes and then rinsed with water. In the study group, EMD was applied, and in the control group, only propylene glycol alginate was applied. Animals were sacrificed 12 weeks after surgery, and block sections were removed, demineralized, and embedded in paraffin. For histomorphometric analysis, three sections from the central area of the defect were selected. Root, surgical defect, epithelial attachment, sulcus, supracrestal connective tissue, ankylosis, and the length and area of new cementum and new bone were measured. RESULTS: No statistically significant differences between the two groups were found for root and defect measures. The remaining parameters were calculated as a percentage of the defect. In the study group, smaller gingival recession (P = 0.05), deeper gingival sulcus (P = 0.05), and shorter junctional epithelium (P = 0.01) were found. New cementum was observed in the study group only (P = 0.02). Ankylosis was six times larger in the control group but not statistically significant. New bone formation was similar in both groups. CONCLUSION: Enamel matrix protein derivative enhanced periodontal healing in this model by reducing gingival recession and junctional epithelium along the root surface and enhancing the formation of new cementum.

Alveolar Process↗

PubMed2006

Experimental intrabony and periodontal defects treated with natural mineral combined with a synthetic cell-binding Peptide in the canine: morphometric evaluations.

BACKGROUND: A synthetic peptide (P-15) analog of collagen added to anorganic bovine bone mineral (ABM) has recently been used as an enhanced bone graft material (ABM/P-15). The objective of this study was to test the contribution of ABM/P-15 in a new putty form (PEP) in two experimental membrane-protected defects: periodontal and intrabony. Its efficacy as filler biomaterial in guided tissue regeneration (GTR) and guided bone regeneration (GBR) procedures was evaluated histologically and morphometrically. METHODS: In the maxillary canines, a facial mucoperiosteal flap was raised bilaterally in nine dogs. Two circular defects, 5 mm in diameter and 2 mm in depth, were made on each side: a fenestrated periodontal on the canine root and an intrabony in the alveolar diastema, anteriorly. PEP particles filled both defects on one side; the contralateral side was blood filled (control). All surgical sites were covered with a bioabsorbable membrane. Histologically, at 4 months, tissue blocks were made using the cutting/grinding non-decalcification method followed by morphometric analysis. In the periodontal fenestration root surface, the linear percentage of new cementum (%CEM), area percentage of new bone (%NB), and residual biomaterial particles (%PEP) were calculated. These same measurements were calculated at the intrabony sites, except cementum. The amount of direct NB to PEP contact was measured to assess the osteoconductivity level (OSC). The Pearson correlation test was used to evaluate any significant relationship between the different measured parameters. RESULTS: In the grafted and non-grafted fenestration root surface defects, %CEM averaged 59.5% and 73.9% (P <0.02), respectively; %NB averaged 36.1% and 31.4%, respectively; and %PEP averaged 20.6%. The mean percentage of OSC was 52.4%. In the intrabony grafted and non-grafted sites, %NB averaged 50.7% and 60.1%, respectively (P <0.02). Residual %PEP averaged 26.1%, and OSC averaged 35.6%. At the intrabony sites, higher %NB and lower %OSC were found compared to the fenestration sites (P <0.001 and P <0.03, respectively). Correlation analysis showed a negative correlation between %NB and %PEP at the fenestration defects. In between the two defect types, %OSC was significantly correlated (P <0.05). CONCLUSIONS: ABM/P-15 putty showed osteoconductive and biocompatible qualities. However, at 4 months in this model, no enhanced regeneration was present compared to a higher CEM and NB growth detected at non-grafted membrane-protected sites.

Absorbable Implants↗

PubMed2005

The amount of newly formed bone in sinus grafting procedures depends on tissue depth as well as the type and residual amount of the grafted material.

OBJECTIVES: Bone replacement substitutes are almost unavoidable in augmentation procedures such as sinus grafting. The objective of the present study was to evaluate the osteoconductive capability of two different scaffold fillers in inducing newly formed bone in this procedure. MATERIAL AND METHODS: Sinus floor augmentation and implant placement were carried out bilaterally in 12 patients. Bovine bone mineral (BBM) was grafted on one side and beta-tricalcium phosphate (beta-TCP) on the contralateral side. Both were mixed (1:1 ratio) with autogenous cortical bone chips harvested from the mandible by a scraper. Hard tissue specimen cores were retrieved from the augmented sites (at the previous window area) at 12 months. Decalcified sections were stained with haematoxylin-eosin and the fraction area of new bone and filler particles was measured. In addition to the effect of the filler on new bone formation, the latter was tested to determine whether it correlated with the tissue depth and residual amount of the grafted material. RESULTS: Bone area fraction increased significantly from peripheral to deeper areas at both grafted sites in all cores: from 26.0% to 37.7% at the beta-TCP sites and from 33.5% to 53.7% at the BBM-grafted sites. At each depth the amount of new bone in BBM sites was significantly greater than that in TCP sites. However, the average area fraction of grafted material particles was similar in both fillers and all depth levels (beta-TCP=27.9-23.2% and BBM=29.2-22.6%, NS). A significant negative correlation was found between bone area fraction and particle area fraction at the middle (p=0.009) and deep (p=0.014) depths in the beta-TCP sites, but not at the BBM sites. CONCLUSION: At 12 months post-augmentation, the two examined bone fillers, beta-TCP and BBM, promoted new bone formation in sinus grafting but the amount of newly formed bone was significantly greater in BBM-grafted sites. However, both exhibited similar residual grafted material area fraction at this healing period. This could imply that BBM possesses better osteoconductive properties.

Adult↗

PubMed2005

Maxillary incisor root resorption after rapid palatal expansion in Felis catus.

Root resorption after rapid palatal expansion (RPE) treatment was found in anchored teeth but has not been studied on non-anchored incisors. This study evaluated root resorption, root tipping, and root proximity of maxillary incisors after RPE treatment. Fourteen cats were divided into treated (n = 10) and untreated (n = 4) groups. The RPE treatment consisted of active, retention, and relapse phases, lasting 25, 60 and 60 d, respectively. Standardized occlusal radiographs were taken to measure tipping and root proximity before and after each treatment phase. Maxillary incisors were analysed histologically by fluorescent microscopy for root resorption. Data was analysed statistically with anova with repeated measures, t-test and Pearson's coefficient of correlation. Root resorption was confined to the first incisors and was 750-fold greater in the treated vs. the control group. Root tipping and root proximity were significantly greater (2.5- and 17-fold, respectively) in the first than in the second maxillary incisor and highly correlated with root resorption (r = -0.927 and 0.723, respectively). This suggests a cause (tipping and root proximity) and effect (root resorption) relationship. Data suggest that first maxillary incisor susceptibility to root resorption during RPE is associated with severe tipping and root proximity.

Animals↗

PubMed2004

Experimental cholestatic liver disease through bile-duct ligation in rats results in skeletal fragility and impaired osteoblastogenesis.

BACKGROUND/AIMS: Patients with cholestatic liver disease have 'low-turnover' osteoporosis. Since we reported that bile-duct ligated (BDL) rats develop bone disease with low bone formation and mass, we examined whether their reduced bone mass results in skeletal fragility, and whether the reduction in osteoprogenitor cells could explain the depressed bone formation. METHODS: Four-week-old rats were pair-fed and subjected to BDL or sham surgery. After 4 weeks, ex vivo bone marrow stromal cell cultures were used to estimate the number of osteoprogenitors and tibial strength was measured by mechanical testing. The serum levels of albumin, bilirubin, alanine amino-transferase (ALT), alkaline phosphatase (ALP) and nitrite were measured. RESULTS: BDL rats had elevated levels of bilirubin, ALT, ALP and nitrite. Tibiae of BDL rats were weaker than those of sham rats, exhibiting lower maximal force (-34%) and stiffness (-37%). The number of mineralized bone-like nodules in cultures from BDL rats was 65% lower than that in cultures from sham-operated rats, attesting to a diminished number of osteoprogenitors. CONCLUSIONS: Skeletal fragility diminished osteoprogenitor pool and elevated plasma levels of nitrite are three additional characteristics of the bone disease that develops in BDL rats, thus increasing the validity of this animal model as representing the human bone disease in patients with cholestatic liver disease.

Animals↗

PubMed2004

Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones.

BACKGROUND & AIMS: Bone loss is a common complication of human inflammatory bowel disease (IBD), but its mechanisms are not understood completely. We investigated bone metabolism in interleukin-10-deficient ( IL-10-/- ) mice, an animal model with IBD features. METHODS: IL-10-/- male mice (8- and 12-weeks-old) and their age-matched wild-type counterparts (C57BL/6J) were studied. Bone mass of the femur was determined by ashing. Tibial cancellous and cortical bone mass and formation was measured by static and dynamic histomorphometry. Biomechanical strength of the femur was tested. Primary bone marrow stromal cell cultures were used to assess osteoblast generation. Serum levels of 25-OH vitamin D 3, insulin-like growth factor-1 (IGF-1), parathyroid hormone, osteocalcin, and deoxy-pyridinoline cross-links were measured. The presence of colitis was determined histologically, and by IL-12 and interferon-gamma (IFN-gamma) secretion from cultured colonic explants. RESULTS: Eight- and 12-week-old IL-10-/- mice developed osteopenia of both cancellous and cortical bone, evidenced by lower femoral ash weight, cancellous bone area and surface, trabecular number, and decreased cortical bone area and width. Osteopenia was associated with mechanical fragility, manifested by decreased stiffness and mechanical load at fracture, and was caused by suppressed bone formation, indicated by decreased cancellous double-labeled surface, mineralizing surface, serum osteocalcin level, and mineralized nodule number in bone marrow stromal cell cultures. IL-10-/- mice with colitis had significantly less bone mass compared with IL-10-/- mice without colitis. CONCLUSIONS: IL-10-/- mice develop the hallmarks of osteoporosis, that is, reduced bone mass, increased mechanical fragility, and suppressed bone formation. The presence of colitis is an important contributor to osteoporosis in IL-10-/- mice.

Animals↗

PubMed2003

Quantitative evaluation of lip symmetry in functional asymmetry.

The objectives of this study were to quantitate lip symmetry/asymmetry from clinical photographs; to demonstrate that asymmetry due to functional side shifts (functional asymmetry) leading to unilateral crossbites including the canines, results from measurable thinning of the upper lip and thickening of the lower lip on the side of the crossbite when viewed in the intercuspal contact position; and to show that orthodontic treatment aimed at eliminating the functional shift and crossbite would achieve lip symmetry, both visually and quantitatively. The study consisted of 26 patients, who were divided into two groups: a study group of 13 patients (eight females, five males, aged 8-17 years) with a functional asymmetry, and a control group of 13 age- and gender-matched subjects with other forms of malocclusion without functional asymmetry. All patients in the study group exhibited unilateral crossbites including the canines in intercuspal contact position. Digitized images of frontal facial photographs were analysed for upper and lower lip symmetry pre- and post-orthodontic treatment. The upper and lower lips were subdivided into four quadrants and the surface area and length of each quadrant were measured and expressed as a percentage of the total surface area/length of the relevant lip. The degree of asymmetry was obtained by calculating the difference in percentage area or length between the two quadrants of each lip. In the study group, the lower lip quadrant on the shift side was enlarged while the contralateral side was reduced (mean area ratio 59.9 to 40.1 per cent, mean length ratio 53.0 to 47.0 per cent). The upper lip demonstrated differences that were smaller and inverse. The controls showed a small difference between the right and left sides (less than 1 per cent). After treatment, both groups displayed visual and quantitative lower and upper lip symmetry, i.e. an area or length of approximately 50 per cent of each quadrant. In absolute values, the control patients had up to 3 per cent asymmetry in area regardless of treatment. The patients in the study group exhibited mean absolute asymmetry of 9.2 per cent in the upper lip and 19.8 per cent in the lower lip. Asymmetry values in the study group were reduced to approximately 3 per cent post-treatment. The absolute values of asymmetry in length of all patients were up to 2 per cent in the control group regardless of treatment. The subjects in the study group exhibited mean absolute asymmetry of 6.3 per cent in the upper lip and 8.6 per cent in the lower lip. Asymmetry values in the study group were reduced post-treatment to approximately 2 per cent. Although asymmetry in the study group could be quantitated using both parameters (lip surface area and lip length), the surface area parameter proved to be a more sensitive tool for measuring lip asymmetry.

Adolescent↗

PubMed2002

Bone mineral metabolism and histomorphometry in rats with cholestatic liver disease.

BACKGROUND: The etiology of osteopenia in cholestatic liver disease is uncertain. An animal model is needed in order to study the efficacy of therapeutic agents. AIMS: In order to characterise the bone disease in rats with cholestatic liver disease. METHODS: Four-month old male Sprague-Dawley bile duct-ligated (BDL) and sham-operated (SO) rats were studied. Twenty-eight days after surgery serum osteocalcin, a bone-formation marker, urinary deoxypyridinoline (DPD) cross-links, a resorption marker, and 25-hydroxyvitamin D3 were determined. Static and dynamic (tetracycline-based) histomorphometric analysis was performed on femurs and tibiae. RESULTS: All BDL rats developed biliary cirrhosis. Bile duct-ligated rats had lower bone mass, reflected in statistically significantly 13.5% lower femoral dry-weight, 16% lower femoral ash-weight, 42.7% lower tibial cancellous bone area and 19% lower trabecular thickness, compared with SO rats. Bile duct-ligated rats exhibited decreased bone formation manifested by statistically significantly 70% lower tetracycline double-labelling, 40% lower mineralising surface, 51% lower bone-formation rate and 47% lower osteocalcin compared with SO rats. Deoxypyridinoline levels were 20% lower in BDL rats. Bile duct-ligated rats had 52% lower serum 25-hydroxyvitamin D3 level, but no significant increase in cortical osteoid area. CONCLUSIONS: Bile duct-ligated rats develop osteopenia characterised by low bone-formation rate, and can be used for studying therapeutic agents for patients with cholestatic liver disease displaying similar bone changes.

Amino Acids↗

PubMedDate not supplied

Biomaterial resorption rate and healing site morphology of inorganic bovine bone and beta-tricalcium phosphate in the canine: a 24-month longitudinal histologic study and morphometric analysis.

PURPOSE: An inorganic xenograft (inorganic bovine bone [IBB]) and a porous alloplast (beta-tricalcium phosphate [beta-TCP]) material were compared at different healing periods in experimental bone defects in dogs. MATERIALS AND METHODS: Six round defects, 5 x 4 mm, were made on the lateral bony mandibular angle in 8 dogs at different times. Two defects were randomly filled with IBB, 2 with beta-TCP, and 2 were left to blood clot. A bi-layer collagen membrane covered 1 defect of each type. Four specimens per treatment group were obtained for each treatment group at 3, 6, 12, and 24 months postoperatively. Morphometric analysis of decalcified (Donath technique) histologic slides was conducted using the measured areas of regenerated bone, grafted particles, and remaining concavity. RESULTS: In IBB sites, complete bone healing was evident at 12 and 24 months, but grafted particles dominated the sites. In beta-TCP sites, only particle remnants remained at 12 months. At 24 months, particles had completely resorbed in both membrane-protected (MP) and uncovered (UC) defects. Data were combined for final analysis since there were no statistically significant differences within each graft material group (MP or UC). Mean bone area fraction increased from 3 to 24 months at all sites. In bone area fraction a statistically significant difference was found between 3 and 6 months in the IBB and beta-TCP groups. IBB sites also showed such significance between 6 and 12 months. A statistically significant difference was found between MP ungrafted sites (42.9%) vs IBB (24.7%) and vs the control (24.8%) at 3 months. At 6 months, beta-TCP bone area fraction (68.8%) was significantly greater than IBB (47.9%) and control (37.5%) sites. At 12 months, beta-TCP bone area fraction (79.0%) was significantly greater than the control (42.5%). At 24 months, beta-TCP bone area fraction (86.5%) was significantly greater than IBB (55.6%) sites. Mean particle area fraction of beta-TCP sites decreased gradually until complete resorption at 24 months. IBB sites showed a significant decrease only between 3 (38.7%) and 6 (29.4%) months. DISCUSSION AND CONCLUSION: Complete bone healing was established in all grafted defects. IBB and beta-TCP are both excellent biocompatible materials. However, at 24 months beta-TCP particles were completely resorbed, whereas IBB particles still occupied a remarkable area fraction without significant resorption beyond 6 months. (More than 50 references.)

Alveolar Bone Loss↗