Selenoproteins containing selenium in the form of selenocysteine are critical for bone remodeling. However, their underlying mechanism of action is not fully understood. Herein, we report the ...identification of selenoprotein W (SELENOW) through large-scale mRNA profiling of receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation, as a protein that is downregulated via RANKL/RANK/tumour necrosis factor receptor-associated factor 6/p38 signaling. RNA-sequencing analysis revealed that SELENOW regulates osteoclastogenic genes. SELENOW overexpression enhances osteoclastogenesis in vitro via nuclear translocation of NF-κB and nuclear factor of activated T-cells cytoplasmic 1 mediated by 14-3-3γ, whereas its deficiency suppresses osteoclast formation. SELENOW-deficient and SELENOW-overexpressing mice exhibit high bone mass phenotype and osteoporosis, respectively. Ectopic SELENOW expression stimulates cell-cell fusion critical for osteoclast maturation as well as bone resorption. Thus, RANKL-dependent repression of SELENOW regulates osteoclast differentiation and blocks osteoporosis caused by overactive osteoclasts. These findings demonstrate a biological link between selenium and bone metabolism.
Background & Aims Decreased levels or function of nucleotide-binding oligomerization domain 2 (NOD2) are associated with Crohn's disease. NOD2 regulates intestinal inflammation, and also is expressed ...by human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), to regulate their differentiation. We investigated whether NOD2 is required for the anti-inflammatory activities of MSCs in mice with colitis. Methods Colitis was induced in mice by administration of dextran sulfate sodium or trinitrobenzene sulfonic acid. Mice then were given intraperitoneal injections of NOD2-activated hUCB-MSCs; colon tissues and mesenteric lymph nodes were collected for histologic analyses. A bromodeoxyuridine assay was used to determine the ability of hUCB-MSCs to inhibit proliferation of human mononuclear cells in culture. Results Administration of hUCB-MSCs reduced the severity of colitis in mice. The anti-inflammatory effects of hUCB-MSCs were greatly increased by activation of NOD2 by its ligand, muramyl dipeptide (MDP). Administration of NOD2-activated hUCB-MSCs increased anti-inflammatory responses in colons of mice, such as production of interleukin (IL)-10 and infiltration by T regulatory cells, and reduced production of inflammatory cytokines. Proliferation of mononuclear cells was inhibited significantly by co-culture with hUCB-MSCs that had been stimulated with MDP. MDP induced prolonged production of prostaglandin (PG)E2 in hUCB-MSCs via the NOD2–RIP2 pathway, which suppressed proliferation of mononuclear cells derived from hUCB. PGE2 produced by hUCB-MSCs in response to MDP increased production of IL-10 and T regulatory cells. In mice, production of PGE2 by MSCs and subsequent production of IL-10 were required to reduce the severity of colitis. Conclusions Activation of NOD2 is required for the ability of hUCB-MSCs to reduce the severity of colitis in mice. NOD2 signaling increases the ability of these cells to suppress mononuclear cell proliferation by inducing production of PGE2.
Oral cancer: A multicenter study Dhanuthai, K; Rojanawatsirivej, S; Thosaporn, W ...
Medicina oral, patología oral y cirugía bucal,
01/2018, Letnik:
23, Številka:
1
Journal Article
Recenzirano
Odprti dostop
To determine the prevalence and clinicopathologic features of the oral cancer patients.
Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to ...2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0.
Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma.
Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.
Osteogenesis and angiogenesis, including cell–cell communication between blood vessel cells and bone cells, are essential for bone repair. Fucoidan is a chemical compound that has a variety of ...biological activities. It stimulates osteoblast differentiation in human mesenchymal stem cells (MSCs), which in turn induces angiogenesis. However, the mechanism by which this communication between osteoblasts and endothelial cells is mediated remains unclear. Thus, the aim of this study was to clarify the relationship between fucoidan‐induced osteoblastic differentiation in MSCs and angiogenesis in endothelial cells. First, the effect was confirmed of fucoidan on osteoblast differentiation in MSCs and obtained conditioned media from these cells (Fucoidan‐MSC‐CM). Next, the angiogenic activity of Fucoidan‐MSC‐CM was investigated and it was found that it stimulated angiogenesis, demonstrated by proliferation, tube formation, migration and sprout capillary formation in human umbilical vein endothelial cells. Messenger ribonucleic acid expression and protein secretion of vascular endothelial growth factor (VEGF) were dramatically increased during fucoidan‐induced osteoblast differentiation and that its angiogenic activities were reduced by a VEGF/VEGF receptor‐specific binding inhibitor. Furthermore, Fucoidan‐MSC‐CM increased the phosphorylation of mitogen‐activated protein kinase and PI3K/AKT/eNOS signalling pathway, and that its angiogenic effects were markedly suppressed by SB203580 and AKT 1/2 inhibitor. Finally, an in vivo study was conducted and it was found that fucoidan accelerated new blood vessel formation and partially promoted bone formation in a rabbit model of a calvarial bone defect. This is the first study to investigate the angiogenic effect of fucoidan‐induced osteoblastic differentiation through VEGF secretion, suggesting the therapeutic potential of fucoidan for enhancing bone repair.
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•Metal-organic frameworks with NH2 were modified to various functional groups.•The modified MOFs showed remarkable performances for adsorptive denitrogenation.•Modified MOF showed the ...best and the second adsorption for indole and quinolone.•The remarkable adsorption could be explained with H-bonding interaction.•The modified MOFs could be easily recycled by ethanol washing.
Removal of nitrogen-containing compounds from fuel is very important for effective utilization of fuel. In this study, a stable metal-organic framework (MOF, here, MIL-125) and its amino form (MIL-125-NH2) were prepared, and the latter one was further modified to get MIL-125 with various functional groups or MIL-125-NH-C(O)-C(O)-OH. The obtained MIL-125s were applied in the adsorption of both neutral indole (IND) and basic quinoline (QUI) from model fuel in order to estimate the possible applications of the MOFs in adsorptive denitrogenation. MIL-125-NH-C(O)-C(O)-OH, MIL-125-VFG (VFG means various functional groups), showed remarkable performances in the adsorptions. Or, MIL-125-VFG showed the highest adsorption capacity for IND, compared with any adsorbent reported so far. The MOF also showed the second highest uptake of QUI, after the protonated polyaniline(5%)@MIL-101. The remarkable performances of MIL-125-VFG could be interpreted with ample active sites for H-bonding, or the adsorption could be explained via H-bonding (IND: H-donor; QUI: H-acceptor). Moreover, the MOF can be easily recycled by ethanol washing. Therefore, MOFs with ample active sites for H-bonding (or with various functional groups) can be suggested as a promising adsorbent for purification of liquid fuel or adsorptive denitrogenation.
Extracellular matrix proteins have been implicated in the regulation of osteoblast differentiation of bone marrow derived mesenchymal stem cells (BMSCs) through paracrine or autocrine mechanisms. In ...the current study, we analyzed the secretory protein profiles of BMSCs grown in osteogenic medium (OSM) and identified SPARC-related modular calcium-binding protein 1 (SMOC1), a member of the SPARC family, as a regulator of osteoblast differentiation of BMSCs. BMSCs with high and low osteogenic potential were grouped and stimulated with OSM, after which conditioned medium was collected and analyzed by LC-MS/MS. We identified 410 proteins, 64 of which were selectively secreted by high osteogenic potential BMSCs. Of these 64 secreted proteins, we selected extracellular matrix proteins for validation in BMSCs undergoing osteoblast differentiation and found that SMOC1 is highly expressed and secreted in BMSCs stimulated with OSM. To examine the role of SMOC1 in osteoblast differentiation, we analyzed the effect of SMOC1 knockdown and overexpression using shRNAs and wild-type cDNA, respectively. Knockdown of SMOC1 significantly inhibited mineralization and the expression of osteoblast differentiation markers, while overexpression of SMOC1 substantially increased the expression of osteoblast differentiation-related genes. Thus, validation of secretome profiling data identified SMOC1 as a putative regulator of osteoblast differentiation of BMSCs.
The present study was conducted to evaluate the efficacy of human dentine grafts for new bone augmentation.
Dentine grafts (demineralized dentine matrix DDM and mineralized dentine matrix MDM) were ...prepared and implanted in rats. Tetracycline was administered twice. Paraffin and resin sections were prepared from the harvested grafts and stained respectively with hematoxylin and eosin (in addition to tartrate acid phosphatase for osteoclasts) and Villanueva. The new bone formation (bone thickness, mineral apposition rate and the bone formation rate) was analyzed in tetracycline-labeled resin sections.
DDM grafts implanted in bone were better able to augment the bone compared to MDM grafts. However, both MDM and DDM failed to induce new bone in ectopic site, they could be considered as alternative autograft substitutes after protocol optimization.
RASSF2 belongs to the Ras‐association domain family (RASSF) of proteins, which may be involved in the Hippo signalling pathway. However, the role of RASSF2 in vivo is unknown. Here, we show that ...Rassf2 knockout mice manifest a multisystemic phenotype including haematopoietic anomalies and defects in bone remodelling. Bone marrow (BM) transplantation showed that Rassf2−/− BM cells had a normal haematopoietic reconstitution activity, indicating no intrinsic haematopoietic defects. Notably, in vitro differentiation studies revealed that ablation of Rassf2 suppressed osteoblastogenesis but promoted osteoclastogenesis. Co‐culture experiments showed that an intrinsic defect in osteoblast differentiation from Rassf2−/− osteoblast precursors likely leads to both haematopoiesis and osteoclast defects in Rassf2−/− mice. Moreover, Rassf2 deficiency resulted in hyperactivation of nuclear factor (NF)‐κB during both osteoclast and osteoblast differentiation. RASSF2 associated with IκB kinase (IKK) α and β forms, and suppressed IKK activity. Introduction of either RASSF2 or a dominant‐negative form of IKK into Rassf2−/− osteoclast or osteoblast precursors inhibited NF‐κB hyperactivation and normalized osteoclast and osteoblast differentiation. These observations indicate that RASSF2 regulates osteoblast and osteoclast differentiation by inhibiting NF‐κB signalling.
The Ras‐binding protein RASSF2 has poorly defined functions in cell‐cycle control and apoptosis, and has been linked to Hippo signalling. Loss of Rassf2 in vivo disrupts osteoblast differentiation via NF‐κB pathway deregulation, with consequent effects on bone formation and haematopoietic development.
Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal ...strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs. We further demonstrate that P2X5 is required for ATP-mediated inflammasome activation and IL-1β production by OCs, and that P2X5-deficient OC maturation is rescued in vitro by addition of exogenous IL-1β. These findings identify a mechanism by which OCs react to inflammatory stimuli, and may identify purinergic signaling as a therapeutic target for bone loss-related inflammatory conditions.
Objectives
Bisphosphonate‐related jaw necrosis (BRONJ) associated with dental implants is a rare but continuously reported complication. To verify clinical and pathological characteristics of BRONJ ...around dental implants, the present study analyzed clinical, radiographic and histopathological findings of these lesions.
Patients and methods
Nineteen patients were diagnosed with osteonecrosis of the jaw associated with dental implants and treated at our institute from 2008 to 2011. The patients' medical history, demographic features, radiographic, and histopathological findings along with information on bisphosphonates (BP) administration were analyzed.
Results
The majority of BRONJ patients associated with dental implants used oral BP for osteoporosis. The patients were divided into two groups: BP initiation before (n = 16) and after (n = 3) implant surgery. Only three patients (15.8%) could be regarded as “implant surgery‐triggered” BRONJ. Many patients (n = 9) showed successful osteointegration after fixture installation to an average of 35 months (11–82 months) until the development of osteonecrosis. The histological features of the lesion showed that the necrotic bone with empty lacunae was infiltrated by inflammatory cells and bacterial colonies. Viable osteocytes were also observed in some areas of the bony specimens. Three types of bone destruction pattern were observed: (i) complete necrosis of the bone around the implant (frozen type), (ii) extensive osteolysis around the implant with or without sequestra (osteolytic type), and (iii) sequestration of bone with an implant maintaining direct implant–bone contact (en block sequestration type). These findings could be existed at the same lesions depending on the degree of local bone destruction and the severity of the infection.
Conclusion
These results and those of others suggested that already osseointegrated dental implants can also cause the osteonecrosis around the implant after BP administration. En block sequestration of bone with implant might be one of the characteristics of implant‐related BRONJ, which is different from peri‐implantitis‐induced bone destruction. The possible role of microcracks in this type of bone destruction needs to be examined further.
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