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OBJECTIVE: The aim of the present study was to objectively assess the degree of residual facial asymmetry after primary treatment of non-syndromic unilateral cleft lip and palate (UCLP) in children and to correlate it with subjective ratings of facial appearance. MATERIALS AND METHODS: Stereophotometry was used to record the faces of 89 children with UCLP for comparison of cleft and non-cleft sides up to 5 years after primary cleft closure. Root mean square values were calculated to measure the difference between the shape of cleft and non-cleft sides of the face and were compared to controls without a cleft lip. The Asher-McDade Aesthetic Index (AMAI) was used for subjective rating of the nasolabial area through 12 laypersons. RESULTS: Children with a cleft lip (CL) showed no significant difference in RMS values compared to controls. Significant differences occurred when the evaluation was limited to the nasolabial area, however only in patients with cleft lip alveolus (CLA) and cleft lip palate (CLAP)(p < 0.001). In contrast, subjective ratings showed significantly higher values for all three cleft severity groups (CL, CLA, CLAP) compared to controls (p < 0.001). There was a non-linear correlation between the RMS (root mean square) values and the AMAI score. CONCLUSIONS: Even non-significant discrete objective deviations from facial symmetry in children after primary closure of UCLP are vigilantly registered in subjective ratings and implemented in the judgement of facial appearance. CLINICAL RELEVANCE: 3D stereophotometry is a usefull tool in monitoring asymmetry in patients with a cleft.
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Labio Leporino , Fisura del Paladar , Asimetría Facial , Humanos , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Femenino , Masculino , Niño , Estética , Preescolar , FotogrametríaRESUMEN
OBJECTIVE: This study was designed to identify changes in the expression of proteins occurring during the progression of oral squamous cell carcinoma (OSCC) and to validate their impact on patient prognosis. MATERIALS AND METHODS: The human OSCC cell line UPCI-SCC-040 was treated in vitro with TGF-ß1, and transcriptome analysis of differentially expressed genes (DEGs) revealed putative candidates relative to untreated cells. The respective protein expression levels of the most important genes were immunohistochemically validated on a tissue microarray (TMA) containing tissue samples from 39 patients with OSCC and were correlated with disease-free survival (DFS) as the primary clinical endpoint. RESULTS: Our univariate Cox proportional hazard regression (CR) analysis revealed significant correlations among positive N stage (local lymph node metastasis, p = .04), stearoyl-CoA desaturase-1 (p < .01), sclerostin (p = .01), and CD137L expression (p = .04) and DFS. Stearoyl-CoA desaturase-1 and sclerostin remained the main prognostic factors (p < .01) in the multiple CR model. CONCLUSION: We identified changes in differentially expressed genes during OSCC progression in vitro and translated the impact of the most deregulated genes on patient prognosis. Stearoyl-CoA desaturase-1 and sclerostin acted as independent prognostic factors in OSCC and could also be interesting candidates for new cancer targeted therapeutic approaches.
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Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Biomarcadores de Tumor/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estearoil-CoA Desaturasa/genéticaRESUMEN
Mesenchymal stem cells are known to exert immunomodulatory effects in inflammatory diseases. Immuneregulatory cells lead to progressive joint destruction in rheumatoid arthritis (RA). Proinflammatory cytokines, such as tumour necrosis factor α (TNF-α) and interleukins (ILs) are the main players. Here, we studied progenitor cells from RA cartilage (RA-CPCs) that are positive for IL-17 receptors to determinate the effects of inflammation on their chondrogenic potenial. IL-17A/F reduced the chondrogenic potential of these cells via the upregulation of RUNX2 protein and enhanced IL-6 protein and MMP3 mRNA levels. Blocking antibodies against IL-17 positively influenced their repair potential. Furthermore, treating the RA-CPCs with the anti-human IL-17 antibody secukinumab or the anti-TNF-α antibody adalimumab reduced the proinflammatory IL-6 protein level and positively influenced the secretion of anti-inflammatory IL-10 protein. Additionally, adalimumab and secukinumab in particular reduced RUNX2 protein to promote chondrogenesis. The amelioration of inflammation, particularly via IL-17 antagonism, might be a new therapeutic approach for enhancing intrinsic cartilage repair mechanisms in RA patients.
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Anticuerpos Bloqueadores/uso terapéutico , Artritis Reumatoide/inmunología , Inmunoterapia/métodos , Interleucina-17/inmunología , Células Madre/inmunología , Adalimumab/administración & dosificación , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Artritis Reumatoide/terapia , Cartílago/patología , Células Cultivadas , Condrogénesis/efectos de los fármacos , Condrogénesis/inmunología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Receptores de Interleucina-17/metabolismo , Células Madre/efectos de los fármacosRESUMEN
The aim of this study was to investigate the role of laminins and nidogen-2 in osteoarthritis (OA) and their potential to support chondrogenic differentiation. We applied immunohistochemistry, electron microscopy, siRNA, quantitative RT-PCR, Western blot, and proteome analysis for the investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. We demonstrate that subunits of laminins appear in OA cartilage and that nidogen-2-null mice exhibit typical osteoarthritic features. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-α1, laminin-α5, and nidogen-2 in their pericellular matrix, and laminin-α1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. Knockdown of nidogen-2 reduced SOX9 expression, whereas it up-regulated RUNX2 expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration.
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Moléculas de Adhesión Celular/metabolismo , Diferenciación Celular/fisiología , Condrocitos/metabolismo , Matriz Extracelular/metabolismo , Laminina/metabolismo , Osteoartritis de la Rodilla/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Unión al Calcio , Condrogénesis/fisiología , Colágeno Tipo II/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Madre/metabolismoRESUMEN
Discoidin domain receptor 1 (DDR-1)-deficient mice exhibited a high incidence of osteoarthritis (OA) in the temporomandibular joint (TMJ) as early as 9 weeks of age. They showed typical histological signs of OA, including surface fissures, loss of proteoglycans, chondrocyte cluster formation, collagen type I upregulation, and atypical collagen fibril arrangements. Chondrocytes isolated from the TMJs of DDR-1-deficient mice maintained their osteoarthritic characteristics when placed in culture. They expressed high levels of runx-2 and collagen type I, as well as low levels of sox-9 and aggrecan. The expression of DDR-2, a key factor in OA, was increased. DDR-1-deficient chondrocytes from the TMJ were positively influenced towards chondrogenesis by a three-dimensional matrix combined with a runx-2 knockdown or stimulation with extracellular matrix components, such as nidogen-2. Therefore, the DDR-1 knock-out mouse can serve as a novel model for temporomandibular disorders, such as OA of the TMJ, and will help to develop new treatment options, particularly those involving tissue regeneration.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Modelos Animales de Enfermedad , Ratones , Osteoartritis/genética , Proteínas Tirosina Quinasas Receptoras/genética , Trastornos de la Articulación Temporomandibular/genética , Articulación Temporomandibular/fisiopatología , Animales , Huesos/citología , Huesos/embriología , Huesos/patología , Proteínas de Unión al Calcio , Moléculas de Adhesión Celular , Células Cultivadas , Condrocitos/citología , Condrocitos/metabolismo , Condrogénesis/fisiología , Colágeno Tipo I/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Receptor con Dominio Discoidina 1 , Matriz Extracelular , Glicoproteínas de Membrana/metabolismo , Ratones Noqueados , Osteoartritis/patología , Proteoglicanos/deficiencia , Interferencia de ARN , ARN Interferente Pequeño , Receptores de Colágeno/metabolismo , Transducción de SeñalRESUMEN
The most common diseases of the joints and its tissues are osteoarthritis and rheumatoid arthritis, with osteoarthritis being anticipated to be the fourth leading cause of disability by the year 2020. To date, no truly causal therapies are available, and this has promoted tissue engineering attempts mainly involving mesenchymal stem cells. The goal of all tissue repairs would be to restore a fully functional tissue, here a hyaline articular cartilage. The hyaline cartilage is the most affected in osteoarthritis, where altered cell-matrix interactions gradually destroy tissue integrity. In rheumatoid arthritis, the inflammatory aspect is more important, and the cartilage tissue is destroyed by the invasion of tumor-like pannus tissue arising from the inflamed synovia. Furthermore, the fibrocartilage of the meniscus is clearly involved in the initiation of osteoarthritis, especially after trauma. Recent investigations have highlighted the role of migratory progenitor cells found in diseased tissues in situ. In osteoarthritis and rheumatoid arthritis, these chondrogenic progenitor cells are involved in regeneration efforts that are largely unsuccessful in diseased cartilage tissue. However, these progenitor cells are interesting targets for a cell-based regenerative therapy for joint diseases.
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Artritis Reumatoide/patología , Movimiento Celular , Condrogénesis/fisiología , Osteoartritis/patología , Células Madre/fisiología , Artritis Reumatoide/terapia , Humanos , Osteoartritis/terapiaRESUMEN
Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabilities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions and migration characteristics. Sclerostin expression was evaluated in clinical cases by immunohistochemistry at the OSCC-jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC-jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The results presented are the first data suggesting a possible involvement of sclerostin in the bone invasion process of OSCC, which deserves further investigation and may be a potential approach for drug-based tumor therapy.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Humanos , Bioensayo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismoRESUMEN
OBJECTIVE: The aim of the present study was to assess the need for secondary palatal corrective surgery in a concept of palate repair that uses a protocol of anterior to posterior closure of primary palate, hard palate and soft palate. METHODS: A data base of patients primarily operated between 2001 and 2021 at the Craniofacial and Cleft Care Center of the University Goettingen was evaluated. Cleft lips had been repaired using Tennison Randall and Veau-Cronin procedures in conjunction with alveolar cleft repair. Cleft palate repair in CLP patients was accomplished in two steps with repair of primary palate and hard palate first using vomer flaps at the age of 10-12 months and subsequent soft palate closure using Veau/two-flap procedures 3 months later. Isolated cleft palate repair was performed in a one-stage operation using Veau/two-flap procedures. Data on age, sex, type of cleft, date and type of surgery, occurrence and location of oronasal fistulae, date and type of secondary surgery performed for correction of oronasal fistula (ONF)and / or Velophyaryngeal Insufficiency (VPI) were extracted. The rate of skeletal corrective surgery was registered as a proxy for surgery induced facial growth disturbance. RESULTS: In the 195 patients with non-syndromic complete CLP evaluated, a total number of 446 operations had been performed for repair of alveolar cleft and cleft palate repair (Veau I through IV). In 1 patient (0,5%), an ONF occurred requiring secondary repair. Moreover, secondary surgery for correction of VPI was required in 1 patient (0,5%) resulting in an overall rate of 1% of secondary palatal surgery. Skeletal corrective surgery was indicated in 6 patients (19,3%) with complete CLP in the age group of 15 - 22 years (n = 31). CONCLUSIONS: The presented data have shown that two-step sequential cleft palate closure of primary palate and hard palate first followed by soft palate closure has been associated with minimal rate of secondary corrective surgery for ONF and VPI at a relatively low need for surgical skeletal correction.
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Labio Leporino , Fisura del Paladar , Procedimientos de Cirugía Plástica , Humanos , Adolescente , Adulto Joven , Adulto , Lactante , Fisura del Paladar/cirugía , Fisura del Paladar/complicaciones , Estudios Retrospectivos , Colgajos Quirúrgicos , Paladar Duro/cirugía , Labio Leporino/cirugía , Fístula Oral/complicaciones , Fístula Oral/cirugía , Resultado del TratamientoRESUMEN
Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, serious, and debilitating disease of unknown cause that can be associated with significant health-related quality of life (HRQOL) impairment. Hematological disease is characterized by a nonhealing exposed jawbone in patients with a history of antiresorptive or antiangiogenic agent use without radiation exposure to the head or neck. Patients and Materials and Methods. This prospective study over the period from May 2020 to December 2021 included a representative sample consisting of 27 patients with at least stage 2 MRONJ lesions who underwent surgical rehabilitation via oral and maxillofacial surgery at the University Medical Center Göttingen, Germany. Quality of life data were collected over a 6-month postoperative period using the Health-Related QOL (SF-12) and Oral Health-Related QOL (OHIP-14) questionnaires. Results: A total of 27 patients considered in the study had a total of 42 MRONJ lesions, corresponding to a mean of 1.56 necroses per patient. MRONJ lesions were downstaged in 85% of the patients. HRQOL was evaluated with the SF-12 questionnaire. Significant improvements were found in six of the eight categories (General Health (p < 0.001), Bodily Pain (p < 0.001), Mental Health (p < 0.001), Vitality (p < 0.001), Role-Emotional (p=0.028), and Social Functioning (p=0.031)). The OHRQOL score also improved significantly after surgical intervention (p < 0.001). Conclusion: With completed surgical therapy, improvements in HRQOL and OHRQOL are measurable.
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BACKGROUND: Changes in the proteome of oral cells during periodontitis have rarely been investigated. This lack of information is partially attributed to the lack of human cell lines derived from the oral cavity for in vitro research. The objective of the present study was to create cell lines from relevant oral tissues and compare protein expression in cells cultured alone and in cells co-cultivated with periodontitis-associated bacterial strains. METHODS: We established human cell lines of gingival keratinocytes, osteoblastic lineage cells from the alveolar bone, periodontal ligament fibroblasts, and cementum cells. Using state-of-the-art label-free mass spectrometry, we investigated changes in the proteomes of these cells after co-cultivation with Aggregatibacter actinomycetemcomitans and Eikenella corrodens for 48 h. RESULTS: Gingival keratinocytes, representing ectodermal cells, exhibited decreased expression of specific keratins, basement membrane components, and cell-cell contact proteins after cultivation with the bacterial strains. Mesodermal lineage cells generally exhibited similar proteomes after co-cultivation with bacteria; in particular, collagens and integrins were expressed at higher levels. CONCLUSIONS: The results of the present study will help us elucidate the cellular mechanisms of periodontitis. Although co-cultivation with two periodontitis-associated bacterial strains significantly altered the proteomes of oral cells, future research is needed to examine the effects of complex biofilms mimicking in vivo conditions.
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The present study aimed to assess the concordance of preoperative and postoperative hard and soft tissues in patients with advanced oral squamous cell carcinoma (OSCC) following virtual surgical planning (VSP) mandibular reconstruction. In the present study, a cohort of 32 patients with OSCC underwent in-house VSP, followed by guided mandibular reconstruction utilizing vascularized free tissue grafts sourced from the fibula or scapula. A morphometric analysis was conducted comparing preoperative and postoperative three-dimensional virtual models to evaluate discrepancies and identify potential risk factors associated with poor reconstruction outcomes. The outcome variables were the differences in root mean square (RMS) and mean surface distance (MSD) resulting from the application of an iterative closest point algorithm to the virtual data. The validity of soft tissue comparison data is limited due to its susceptibility to various confounding variables. The present study conducted a comprehensive re-evaluation of these variables. High tumor stage, positive N status and the use of adjuvant therapy contributed to more noticeable differences in preoperative and postoperative facial soft tissue appearance. The accuracy of postoperative bone reconstruction results was higher in patients who underwent neomandibular formation using a fibular graft compared with those who received a scapular graft. Preoperative and postoperative soft tissue analyses were conducted for comparison. The MSD showed a deviation of 3.2 mm (± 2.0 mm SD; range 1.3-9.5 mm), whereas the RMS was 5.3 (± 2.9 SD; range 2.1-14). In conclusion, in-house VSP and guided mandibular reconstructions can yield clinically accurate results, preserving patient appearance and offering the advantage of rapid feasibility.
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OBJECTIVE: The aim of this study was to investigate the roles of SMURF1 and SMURF2 in progenitor cells from the human knee in late-stage osteoarthritis (OA). DESIGN: We applied immunohistochemistry, immunocytochemistry, RNAi, lentiviral transfection, and Western blot analysis. We obtained chondrogenic progenitor cells (CPCs) from the articular cartilage and meniscus progenitor cells (MPCs) from the nonvascularized part of the meniscus. RESULTS: SMURF1 and SMURF2 appeared in both osteoarthritic tissues. CPCs and MPCs exhibited comparable amounts of these proteins, which influence the balance between RUNX2 and SOX9. The overexpression of SMURF1 reduced the levels of RUNX2, SOX9, and TGFBR1. The overexpression of SMURF2 also reduced the levels of RUNX2 and TGFBR1, while SOX9 levels were not affected. The knockdown of SMURF1 had no effect on RUNX2, SOX9, or TGFBR1. The knockdown of SMURF2 enhanced RUNX2 and SOX9 levels in CPCs. The respective protein levels in MPCs were not affected. CONCLUSIONS: This study shows that SMURF1 and SMURF2 are regulatory players for the expression of the major regulator transcription factors RUNX2 and SOX9 in CPCs and MPCs. Our novel findings may help elucidate new treatment strategies for cartilage regeneration.
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Cartílago Articular , Menisco , Osteoartritis , Cartílago Articular/metabolismo , Condrogénesis , Humanos , Menisco/metabolismo , Osteoartritis/metabolismo , Células Madre/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Oral cancer therapy is associated with a loss in health-related quality of life (HRQOL) and can also lead to post-traumatic growth (PTG). The current study analyzed the relationship between HRQOL, PTG and influencing clinical factors after treatment. The coherent clinical data of 15 patients were retrospectively analyzed over a 1-year study period. HRQOL and PTG were studied using the University of Washington Quality of Life Version 4 (UW-QOL v4) and Posttraumatic Growth Inventory (PTGI) questionnaires. The results revealed that HRQOL was significantly decreased in a pre- to postoperative manner (P=0.011). Sex demonstrated a nearly significant effect on HRQOL (P=0.058). PTG was experienced the most after surgery, and continuously decreased over the 1-year study period. Patient age had a significant effect on PTG (P=0.040). A significant correlation was also established between HRQOL and PTG (P<0.05). HRQOL and PTG are important influencing factors during postoperative tumor follow-up care and should be simultaneously recorded to address individual patient needs and improve quality of treatment.
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This study investigated the cotransplantation of bone marrow mesenchymal stromal cells (BMSC) and human umbilical cord endothelial cells (HUVEC), and evaluated their contribution to vascular and bone tissue engineering in vivo. To evaluate the success of osteogenic differentiation and timely vascularization of different osteoconductive scaffolds in vivo, we transferred BMSC and HUVEC pre-cultivated calcium carbonate (CaCO3) and hydroxylapatite (HA) matrices into immunocompromised RNU-rats, and analyzed mineralization, expression of osteopontin, and vascular integration via new vessel formation. After in vivo transplantation, pre-cultivated scaffolds demonstrated overall improved mineralization of 44% for CaCO3 (p = 0.01, SD ± 14.3) and 34% for HA (p = 0.001, SD ± 17.8), as well as improved vascularization of 5.6 vessels/0.1 mm2 on CaCO3 (p < 0.0001, SD ± 2.0) and 5.3 vessels/0.1 mm2 on HA (p < 0.0001, SD ± 2.4) compared with non-pre-cultivated controls. However, no significant differences between the implantation of BMSC-only, HUVEC-only, or BMSC + HUVEC cocultures could be observed. There is an increasing demand for improved bone regeneration in tissue engineering. Cotransplantation of mesenchymal stromal cells and endothelial cells often demonstrates synergistic improvements in vitro. However, the benefits or superiority of cotransplantation was not evident in vivo and so will require further investigation.
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Células Madre Mesenquimatosas , Animales , Carbonato de Calcio , Diferenciación Celular , Durapatita , Células Endoteliales , Células Endoteliales de la Vena Umbilical Humana , Osteogénesis , Ratas , Células del Estroma , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
INTRODUCTION: The aim of this study was to investigate the effect of dihydrotestosterone (DHT), 17-ß-estrogen (E2), genistein (GEN) and equol (EQ) on bone remodeling and bone morphology during healing of osteoporotic male rat tibiae. MATERIALS AND METHODS: 180 Sprague-Dawley male rats were divided in 5 groups of 36 animals. After orchidectomy (ORX) and development of osteoporosis, trepanation of the tibia was performed. Until the time of trepanation all groups received soya free food (SF), then food change occurred and treatment started. At day 95, 102 and 151, samples were taken and histomorphometry was performed to analyze changes in bone structure under treatment. At day 33 and 70 all animals received calcein respective alizarin for polychrome bone labeling. RESULTS: The cortical bone was particularly affected. Treatment with DHT and E2 led to a significant long-term expansion of the thickness of the diaphyseal cortical bone, while the phytoestrogens EQ and GEN only had a positive short-term effect in this area. Only E2 preserved the trabecular bone for a limited time. In all groups, periosteal and endosteal bone areas showed the highest bone formation activity. The osteoporotic male injured bone shows a shift in mineral apposition rate (MAR) from periosteal to endosteal bone in the SF, DHT and E2 groups but not in the GEN and EQ phytohormones groups. An MAR decrease in trabecular bone formation was observed at day 70 in all groups except the E2 group. CONCLUSION: We conclude from our results that healing of cortical bone defects in a rat model of male osteoporosis are mainly influenced by the estrogen pathway. Nevertheless, effects via purely androgenic mechanisms can also be demonstrated. The role of a phytohormone therapy is only marginal and if only useful for a short-term supportive approach. The role of the periosteal to endosteal shift during male osteoporotic bone healing needs to be further examined.
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Osteoarthritis (OA) is the most common chronic joint disease and leads to the degradation of the extracellular matrix by an imbalance between anabolic and catabolic processes. TGF-ß3 (transforming growth factor beta-3) and epidermal growth factor (EGF) influence the osteochondrogenic potential of chondrocytes. In this study, we compared the expression of mediators and receptors in the TGF-ß3 and EGF pathways, as well as biglycan (BGN), in healthy and diseased chondrocytes. Furthermore, we used chondrogenic progenitor cells (CPCs) for in vitro stimulation and knockdown experiments to elucidate the effects of TGF-ß3 and EGF on the chondrogenic potential. Our results demonstrate that the expression of TGF-beta receptor type-1 (TGFBRI) and epidermal growth factor receptor (EGFR) is altered in diseased chondrocytes as well as in CPCs. Moreover, TGF-ß3 and EGF stimulation influenced the expression levels of BGN, SRY (sex determining region Y)-box 9 (SOX9), and Runt-related transcription factor 2 (RUNX2) in CPCs. Therefore, changes in TGFBRI and EGFR expression likely contribute to the degenerative and regenerative effects seen in late stages of OA.
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Biglicano/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Factor de Crecimiento Epidérmico/genética , Regulación de la Expresión Génica , Factor de Transcripción SOX9/genética , Células Madre/metabolismo , Factor de Crecimiento Transformador beta3/genética , Biomarcadores/metabolismo , Diferenciación Celular , Condrogénesis , Femenino , Humanos , Masculino , Transducción de Señal , Células Madre/citologíaRESUMEN
BACKGROUND: Clefts in newborns are associated with severe morphological and functional impairment. Especially the lip is of importance as if the treatment result is unsatisfactory, it can lead to psychological changes in the patient. Different operative procedures have been developed over the last decades. The aim of the presented study was the comparison of the surgical techniques according to Millard and Pfeifer regarding the temporal development of the postoperative symmetry of the lip height and mouth width. METHODS: Digitized photographs of patients from the department of oral and maxillofacial surgery at the University of Göttingen were evaluated from 1979 to 1996. With a video analysis program, the lip height and mouth width were analyzed regarding the symmetry. We demonstrated the symmetry values over a period of 8 years in order to show the influence of growth on postoperative results. RESULTS: The development of the vertical symmetry of the Philtrum and the lip vermillion on the cleft side in comparison to the healthy side behaves differently depending on Pfeifer and Millard. The lip height of the cleft lip was shorter in both techniques than on the healthy side, but Pfeifer's difference was significantly more pronounced. The lip vermillion height on the cleft side was slightly shorter in the Millard group and markedly larger in the Pfeifer group. Both techniques can achieve good symmetry results for the vertical dimension of the lip. According to Pfeifer, the development of the horizontal dimension on the cleft side is bigger within the first 4 years than on the healthy side; according to the Millard technique, the horizontal development is smaller. These differences are greater within the first 6 years and approach between the 6th and 8th year. CONCLUSIONS: The Millard technique demonstrates better results concerning the philtrum and vermillion symmetry during growth within the first 6 years. Over the whole study period, growth corrects the philtrum and vermillion symmetry within the Pfeifer group.
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Periodontitis refers to inflammatory disease of the periodontal structures (the gingiva, dental cementum, periodontal ligament (PDL) and alveolar bone) that ultimately leads to their destruction. Whereas collagens are well-examined main components of the periodontium, little is known about the other structural proteins that make up this tissue. The aim of this study was to identify new extracellular matrix (ECM) components, including fibulins and matrilins, in the periodontium of mice. After sacrificing 14 mice (Sv/129 strain), jaws were prepared. Each tissue sample contained a molar and its surrounding alveolar bone. Immunohistochemistry was carried out on paraffin-embedded sections. Our results show that mice exhibit fibulin-3, -4 and -5 and matrilin-1, -2, -3 and -4 in PDL and in blood vessels of alveolar bone and PDL as well as in the pericellular matrix of osteocytes and cementocytes. In dental cementum, only fibulin-4 is expressed. For the first time, we show that fibulin-3, -4 and -5 and matrilin-1, -2, -3 and -4 are essential components of the periodontal tissues. Our findings indicate an association of these proteins with collagens and oxytalan fibers that might be of future interest in regenerative periodontitis therapy.
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Proteínas de Unión al Calcio/metabolismo , Proteínas Matrilinas/metabolismo , Periodoncio/metabolismo , Animales , Cemento Dental/metabolismo , Matriz Extracelular/metabolismo , Técnicas para Inmunoenzimas , Ratones , Periodoncio/citologíaRESUMEN
AIM: The present in vitro study was designed to evaluate the surface characteristics, biocompatibilities and antimicrobial effects of experimental titanium implant surfaces, coated by nanocrystalline silver, copper, and bismuth. Biocompatible and antimicrobial implant modifications could result in reduced biofilm formation on implant surfaces and therefore in less periimplant inflammation. FINDINGS: Titanium discs (thickness 1 mm and 12 mm in diameter) were coated by pulsed magnetron-sputtering of nanocrystalline metals (bismuth, copper, and silver). Bismuth coatings revealed higher surface roughness values in comparison to silver and copper coatings via atomic force microscopy. Ion release after 168 h in culture medium was analyzed by inductively coupled plasma-mass spectrometry and showed significant different amounts of released copper (>120 000 µg/L), silver (550 µg/L) or bismuth (80 µg/L). No cytotoxic effect on HaCaT cell proliferation was detected on the uncoated Ti/TiO2 reference surfaces, the bismuth coatings and silver coatings. In contrast, copper-coated discs showed a strong cytotoxic effect. All three coatings exhibited antimicrobial effects by trend in the fluorometric Resazurin testing and significant localized antibacterial effects in live/dead microscopy after incubation of the specimens for 150 min in bacterial solution of S. epidermidis. CONCLUSIONS: The tested metallic implant coatings (silver and bismuth) allowed surface modifications that may improve therapeutic approaches to biofilm prevention on dental implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1571-1579, 2016.
Asunto(s)
Antiinfecciosos/química , Bismuto/química , Condrocitos/metabolismo , Materiales Biocompatibles Revestidos/química , Ensayo de Materiales , Nanopartículas/química , Staphylococcus epidermidis/crecimiento & desarrollo , Línea Celular , Condrocitos/citología , HumanosRESUMEN
Degeneration of the knee joint during osteoarthritis often begins with meniscal lesions. Meniscectomy, previously performed extensively after meniscal injury, is now obsolete because of the inevitable osteoarthritis that occurs following this procedure. Clinically, meniscus self-renewal is well documented as long as the outer, vascularized meniscal ring remains intact. In contrast, regeneration of the inner, avascular meniscus does not occur. Here, we show that cartilage tissue harvested from the avascular inner human meniscus during the late stages of osteoarthritis harbors a unique progenitor cell population. These meniscus progenitor cells (MPCs) are clonogenic and multipotent and exhibit migratory activity. We also determined that MPCs are likely to be controlled by canonical transforming growth factor ß (TGF-ß) signaling that leads to an increase in SOX9 and a decrease in RUNX2, thereby enhancing the chondrogenic potential of MPC. Therefore, our work is relevant for the development of novel cell biological, regenerative therapies for meniscus repair.