Levels In Bone Research Articles

Effect of artesunate on cardiovascular complications in periodontitis in a type I diabetes rat model and related mechanisms.

Both cardiovascular disease and periodontitis are complications of diabetes that have a great impact on human life and health. Our previous research found that artesunate can effectively improve cardiovascular disease in diabetes and has an inhibitory effect on periodontal disease. Therefore, the present study aimed to explore the potential therapeutic possibility of artesunate in the protection against cardiovascular complications in periodontitis with type I diabetes rats and to elucidate the possible underlying mechanisms. Sprague‒Dawley rats were randomly divided into the healthy, diabetic, periodontitis, diabetic with periodontitis, and artesunate treatment groups (10, 30, and 60mg/kg, i.g.). After artesunate treatment, oral swabs were collected and used to determine changes in the oral flora. Micro-CT was performed to observe changes in alveolar bone. Blood samples were processed to measure various parameters, while cardiovascular tissues were evaluated by haematoxylin-eosin, Masson, Sirius red, and TUNEL staining to observe fibrosis and apoptosis. The protein and mRNA expression levels in the alveolar bone and cardiovascular tissues were detected using immunohistochemistry and RT‒PCR. Diabetic rats with periodontitis and cardiovascular complications maintained heart and body weight but exhibited reduced blood glucose levels, and they were able to regulate blood lipid indicators at normal levels after artesunate treatment. The staining assays suggested that treatment with 60mg/kg artesunate has a significant therapeutic effect on myocardial apoptotic fibrosis. The high expression of NF-κB, TLR4, VEGF, ICAM-1, p38 MAPK, TGF-β, Smad2, and MMP9 in the alveolar bone and cardiovascular tissue in the type I diabetes and type I diabetes with periodontitis rat models was reduced after treatment with artesunate in a concentration-dependent manner. Micro-CT showed that treatment with 60mg/kg artesunate effectively alleviated alveolar bone resorption and density reduction. The sequencing results suggested that each model group of rats had vascular and oral flora dysbiosis, but artesunate treatment could correct the dysbacteriosis. Periodontitis-related pathogenic bacteria cause dysbiosis of the oral and intravascular flora in type I diabetes and aggravate cardiovascular complications. The mechanism by which periodontitis aggravates cardiovascular complications involves the NF-κB pathway, which induces myocardial apoptosis, fibrosis, and vascular inflammation.

The Effect of Omega-9 on Bone Viscoelasticity and Strength in an Ovariectomized Diet-Fed Murine Model.

Few studies have investigated the effect of a monosaturated diet high in ω-9 on osteoporosis. We hypothesized that omega-9 (ω-9) protects ovariectomized (OVX) mice from a decline in bone microarchitecture, tissue loss, and mechanical strength, thereby serving as a modifiable dietary intervention against osteoporotic deterioration. Female C57BL/6J mice were assigned to sham-ovariectomy, ovariectomy, or ovariectomy + estradiol treatment prior to switching their feed to a diet high in ω-9 for 12 weeks. Tibiae were evaluated using DMA, 3-point-bending, histomorphometry, and microCT. A significant decrease in lean mass (p = 0.05), tibial area (p = 0.009), and cross-sectional moment of inertia (p = 0.028) was measured in OVX mice compared to the control. A trend was seen where OVX bone displayed increased elastic modulus, ductility, storage modulus, and loss modulus, suggesting the ω-9 diet paradoxically increased both stiffness and viscosity. This implies beneficial alterations on the macro-structural, and micro-tissue level in OVX bone, potentially decreasing the fracture risk. Supporting this, no significant differences in ultimate, fracture, and yield stresses were measured. A diet high in ω-9 did not prevent microarchitectural deterioration, nevertheless, healthy tibial strength and resistance to fracture was maintained via mechanisms independent of bone structure/shape. Further investigation of ω-9 as a therapeutic in osteoporosis is warranted.

Abutment-Bar Structure Connection Geometry: An Important Design Parameter for Implant-Supported Bar-Retained Overdentures With Cantilever Extension.

When extended distally due to higher loading in the posterior region, implant-supported bar-retained overdentures with cantilever bar extension exhibit greater bending moments on the implants closest to the cantilever bar and increased stresses in the overdenture components. In this study, a new abutment-bar structure connection was introduced to minimize undesired bending moments and reduce the resulting stresses by increasing the rotational mobility of the bar structure on the abutments. Copings of the bar structure were modified to have 2 spherical surfaces, sharing the same center, located at the centroid of the top surface of the coping screw head. The new connection design was applied to a 4 implant-supported mandibular overdenture to create a modified overdenture. Both the classical and modified models had bar structures with cantilever extensions in the first and second molar areas and were analyzed for deformation and stress distribution using finite element analysis, which was also conducted for both the overdenture models without cantilever bar extensions. Real-scale prototypes of both models with cantilever extensions were manufactured, assembled on implants embedded in polyurethane blocks, and subjected to fatigue testing. Both models' implants were subjected to pullout testing. The new connection design increased the rotational mobility of the bar structure, minimized the bending moment effects, and reduced the stress levels in the peri-implant bone and overdenture components, whether cantilevered or not. Our results verify the effects of rotational mobility of the bar structure on the abutments and validate the importance of the abutment-bar connection geometry as a design parameter.

The Influence of Environmental Exposure to Heavy Metals on the Occurrence of Selected Elements in the Maxillary Bone.

The elemental composition of the body's calcified tissues may reflect the environmental exposure of the population to heavy metals. The aim of the study was to assess whether the elemental composition of the maxillary bone from individuals belonging to a given population reflects the environmental exposure of this population to lead and cadmium. The research material consisted of cortical bone from the anterolateral walls of the maxilla collected from 126 patients during Caldwell-Luc maxillary sinus surgery on residents of two cities differing in terms of the lead and cadmium pollution of the natural environment. The content levels of lead, cadmium, iron, manganese, chromium, copper, and iron were determined by using atomic absorption spectrophotometry. The content levels of lead and cadmium in the samples of the maxillary bones of residents of Bielsko-Biala were 3.26 ± 2.42 µg/g and 0.74 ± 0.38 µg/g, respectively, whereas in the samples from the residents of Katowice, they were 7.66 ± 2.79 µg/g and 1.12 ± 0.08 µg/g, respectively. It was found that the lead and cadmium levels in the maxillary bone corresponded to the environmental exposure to these heavy metals in the place of residence, which was proven here via the example of the residents of two cities with different concentrations of these heavy metals in the air over long time periods. Additionally, higher content levels of essential metals such as manganese, chromium, copper, and iron are characteristic of the maxillary bone samples of residents of the area that is more polluted with heavy metals.

Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice.

Osteoporosis is evident in postmenopausal women and is an osteolytic disease characterized by bone loss that further increases the susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. Edible Cirsium setidens contains various polyphenols of linarin, pectolinarin, and apigenin with antioxidant and hepatoprotective effects. This study aimed to determine whether Cirsium setidens water extracts (CSEs), the component linarin, and its aglycone acacetin blocked ovariectomy (OVX)-induced bone loss. This study employed OVX C57BL/6 female mice as a model for postmenopausal osteoporosis. CSEs, acacetin, or linarin was orally administrated to OVX mice at a dose of 20 mg/kg for 8 weeks. Surgical estrogen loss in mice for 8 weeks reduced bone mineral density (BMD) of mouse femur and serum 17β-estradiol level and enhanced the serum receptor activator of NF-κB ligand/osteoprotegerin ratio with uterine atrophy. CSEs and linarin reversed such adverse effects and enhanced femoral BMD in OVX mice. Oral administration of CSEs and linarin attenuated tartrate-resistant acid phosphate activity and the induction of αvβ3 integrins and proton suppliers in resorption lacunae in femoral bone tissue of OVX mice. In addition, CSEs and linarin curtailed the bone levels of cathepsin K and matrix metalloproteinase-9 responsible for osteoclastic bone resorption. On the other hand, CSEs and linarin enhanced the formation of trabecular bones in estrogen-deficient femur with increased induction of osteocalcin and osteopontin. Further, treatment with CSEs and linarin enhanced the collagen formation-responsive propeptide levels in the circulation along with the increase in the tissue non-specific alkaline phosphatase level in bone exposed to OVX. Supplementing CSEs, acacetin, or linarin to OVX mice elevated the formation of collagen fibers in OVX trabecular bone, evidenced using Picrosirius red staining. Accordingly, CSEs and linarin were effective in retarding osteoclastic bone resorption and promoting osteoblastic bone matrix mineralization under OVX conditions. Therefore, linarin, which is abundant in CSEs, may be a natural compound for targeting postmenopausal osteoporosis and pathological osteoresorptive disorders.

Avaliação dos níveis de fósforo sérico e ósseo em búfalas (Bubalus bubalis) antes e após suplementação com mistura mineral seletiva

ABSTRACT: This study aimed to evaluate phosphorus (P) concentration in serum and bone, the percentage of ash and the specific bone density of buffaloes on Ilha de Marajó before and after mineral supplementation. For this study, 14 crossbred buffaloes of Murrah and Mediterranean descent aged between 18 and 36 months were used. The average values of P before supplementation in serum and bone, the percentage of bone ash and the specific bone density were 5.68mg/dL±1.18, 16.53%±0.53, 59.95%±1.96 and 1.52g/cm3±0.32, respectively, which demonstrated P deficiency in animals raised on Ilha de Marajó. After supplementation with P for a period of seven months, the values were 6.61mg/dL±0.87, 16.90%±0.56 and 60.30%±0.95 and 1.71g/cm3±0.21, respectively. These results showed a significant increase in P concentration in blood serum, specific bone density and percentage of P in ash (P<0.05), but there was no significant increase in the percentage of ash. The average increase in P in the serum and ash did not reach normal levels in all animals; however, 28.6% of the animals had normal values of P in serum and 50% in the ash, and 64.3% had normal specific bone density values. The nonre-establishment, in some of the animals, of the variables of P serum and bone after supplementation for seven months may have occurred as a result of the low intake of the mineral mixture and by the low concentration of P in the Brachiaria brizantha cv. Marandu used for feeding animals during the experiment.

Pharmacokinetics and Pharmacodynamics (PK/PD) of Corallopyronin A against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a World Health Organization’s high priority pathogen organism, with an estimated > 100,000 deaths worldwide in 2019. Thus, there is an unmet medical need for novel and resistance-breaking anti-infectives. The natural product Co-rallopyronin A (CorA), currently in preclinical development for filariasis, is efficacious against MRSA in vitro. In this study, we evaluated the pharmacokinetics of CorA after dosing in mice. Furthermore, we determined compound concentrations in target compartments, such as lung, kidney and thigh tissue, using LC-MS/MS. Based on the pharmacokinetic results, we evaluated the pharmacodynamic profile of CorA using the standard neutropenic thigh and lung infection models. We demonstrate that CorA is effective in both standard pharmacodynamic models. In addition to reaching effective levels in the lung and muscle, CorA was detected at high levels in the thigh bone. The data presented herein encourage the further exploration of the additional CorA indications treatment of MRSA- and methicillin-sensitive S. aureus- (MSSA) related infections.

90Sr and stable element levels in bones of brown bears: long-term trends in bear populations from Croatia and Poland.

The aim of this study was to investigate the temporal trends and geographical differences in 90Sr and stable element (Ba, Ca, Mn, Sr, Pb, Zn) levels in the bones of Croatian and Polish brown bear (Ursus arctos) populations. Experimental data suggest that in the decades after nuclear weapon tests and the Chernobyl accident, 90Sr bone activity concentrations decreased from 352 to 11Bqkg-1 in the Croatian bear population (period 1982-2015) and from 831 to 27Bqkg-1 in Polish bears (period 1962-2020). Calculated effective and ecological half-lives were 9 and 13years for Croatian bears, and 15 and 31years for Polish bears, respectively. Different temporal trends were noted in levels of Ba, Mn, Pb and Zn between the two countries with majority of bones having lower Pb, Sr and Zn in Croatian than in Polish bears. Estimated values for the soil-to-bear transfer of 90Sr were the same order of magnitude in the studied populations. Contrary to this, the estimated transfer of stable Sr was an order of magnitude lower for the Croatian bear population compared to Polish bears. The observed differences in soil-to-bear transfer between stable Sr and 90Sr found for Croatian bears might suggest the need for careful consideration on the use of stable Sr data as an analogue for 90Sr. To our knowledge, this is the first study that analysed 90Sr activity in tissue of brown bears. As such, it provides insight into the fate and behaviour of one of the most relevant anthropogenic radionuclides at the top of the food chain.

Analysis of Protein Levels in Cow Bones from Kaledo Waste from Palu City Central Sulawesi

Kaledo (donggala ox leg) is one of the famous culinary in Central Sulawesi. The number of restaurants that provide kaledo menus causes problems, due to the lack of utilization of the bone waste, causing problems in the environment. People still don't know that beef bones still contain protein. Protein serves as a form of new tissue during the growth and development of the body. This study aims to determine the protein content of beef bones from kaleo waste from the city of Palu, Central Sulawesi, which was taken randomly from a kaledo restaurant. Determination of protein content in beef bones from kale waste using the Kjeldhal method. In the results of calculations that have been carried out with three repetitions, it was found that the protein content in Repetition1 was 3.85%, Repetition2 was 3.59% and Repetition3 was 4.2%. The average protein content of beef bones from kale waste is 3.88%. The results of this study are expected to be a source of information about the protein content contained in beef bones from kaleo waste and can be used further as a substance in the utilization of bone waste.

A multi-model approach to predict efficacious clinical dose for an anti-TGF-β antibody (GC2008) in the treatment of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited bone dysplasias characterized by reduced skeletal mass and bone fragility. Although the primary manifestation of the disease involves the skeleton, OI is a generalized connective tissue disorder that requires a multidisciplinary treatment approach. Recent studies indicate that application of a transforming growth factor beta (TGF-β) neutralizing antibody increased bone volume fraction (BVF) and strength in an OI mouse model and improved bone mineral density (BMD) in a small cohort of patients with OI. In this work, we have developed a multitiered quantitative pharmacology approach to predict human efficacious dose of a new anti-TGF-β antibody drug candidate (GC2008). This method aims to translate GC2008 pharmacokinetic/pharmacodynamic (PK/PD) relationship in patients, using a number of appropriate mathematical models and available preclinical and clinical data. Compartmental PK linked with an indirect PD effect model was used to characterize both pre-clinical and clinical PK/PD data and predict a GC2008 dose that would significantly increase BMD or BVF in patients with OI. Furthermore, a physiologically-based pharmacokinetic model incorporating GC2008 and the body's physiological properties was developed and used to predict a GC2008 dose that would decrease the TGF-β level in bone to that of healthy individuals. By using multiple models, we aim to reveal information for different aspects of OI disease that will ultimately lead to a more informed dose projection of GC2008 in humans. The different modeling efforts predicted a similar range of pharmacologically relevant doses in patients with OI providing an informed approach for an early clinical dose setting.

Regulatory Effect of Thyroxine on Calcium and Phosphorus Metabolism in Tissues of Common Indian Toad

Thyroxine (T4) plays a vital role in the metabolic processes of animals. It influences the storage and mobilisation of minerals and their utilisation according to the requirement of the body. It is also involved in the early development of vertebrates, especially in amphibian metamorphosis. It has shown anabolic and catabolic effects at a lower dose and higher dose, respectively. The present study aims to identify the role of thyroxine in regulating calcium and phosphorous metabolism in the blood, muscle and bone tissues of Bufo melanostictus. Toads of various sizes and different age groups were chosen, showing a positive correlation between body weight and snout to vent length, indicating overall continuous growth as observed for a large number of poikilothermic animals. As per an earlier report, thyroxine has been shown to have a direct catabolic effect on bone mineral homeostasis leading to an increase in bone mineral resorption and calcium loss through the kidney. Results of the present study indicate that thyroxine treatment in Bufo melanostictus caused depletion of calcium and phosphorous in muscle and bone, while their level increased in the serum at both doses (0.5 μg/gm and 2 μg/gm) during short term i.e. a one-day T4 treatment. Such results are very much consistent with many of the earlier obscurations that, T4 causes an increase in serum calcium and phosphorous levels, while their level in muscle and bone decreased. When the level of these two minerals falls in the serum due to any other condition, the bone resorption under the influence of thyroxine maintains the concentration in serum, consequently, there is a loss in bone density due to resorption and in muscle due to utilisation. However, if the exogenous supply is adequate, the loss caused as above is compensated for, in both bone and muscle.

Comparison of levels of toxic trace elements in two most common spinal pathologies in three different tissues

Aim: The toxic trace element levels in serum, bone (lamina), and intervertebral disc tissues of patients with lumbar spinal stenosis and lumbar herniated nucleus pulposus (HNP) which are the two most common spinal pathologies were determined, and it was investigated whether they have a role in the pathophysiology of these pathologies. Materials and methods: Cadmium (Cd), aluminium (Al), arsenic (As), mercury (Hg), and lead (Pb) levels in serum, intervertebral disc, and bone (lamina) tissue of patients with HNP (=20) and 30 with lumbar spinal stenosis (LSS) (n=30) were determined by Inductively Coupled Plasma Mass Spectrometry technique. Results: LDH group Cd serum level was found to be significantly higher than LSS group Cd serum level (p=0.024). The Al disc level in the HNP group was found to be significantly higher than the Al disc level in the LSS group (p=0.038). While As serum level increased in LDH group, it was determined that As bone level increased very significantly (r= 0.699, p=0.001). In the LSS group, it was determined that the Hg disc level increased significantly as the Hg serum level increased (r=0.608, p<0.01). On the other hand, as the Hg serum level increased in the LDH group, the Hg disc level also decreased significantly (r= -0.579, p<0.01). Conclusion: The difference in toxic trace element levels seen in these pathologies has been discussed in terms of possible causes in light of current literature. The findings of our study support the hypothesis that toxic trace elements may be effective in lumbar disc degeneration.

MicroRNA-26b regulates BMSC osteogenic differentiation of TMJ subchondral bone through β-catenin in osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease of the joint. The early manifestations of TMJ-OA are abnormal remodeling of condylar subchondral bone. In bone tissue, bone marrow mesenchymal stem cells (BMSCs) and osteoblasts play important roles in the differentiation and maturation of most hematopoietic cells. MicroRNA-26b (miR-26b) is upregulated during the osteogenesis of BMSCs, and miR-26b overexpression leads to the activation of β-catenin and the enhancement of osteogenesis and cartilage formation. However, the pathologic mechanism remains unclear. In the present study, we used a rat model with OA-like changes in the TMJ induced by experimental unilateral anterior crossbite (UAC) and found that the level of miR-26b was markedly lower in BMSCs from the subchondral bones of UAC rats than in those from sham control rats. MiR-26b overexpression by agomiR-26b increased condylar subchondral bone osteogenesis in UAC rats. Notably, although agomiR-26b primarily affected miR-26b levels in the subchondral bone (but not in cartilage or the synovium), the overexpression of miR-26b in BMSCs in UAC rats largely rescued OA-like cartilage degradation, while the inhibition of miR-26b in BMSCs exacerbated cartilage degradation in UAC rats. We measured the expression levels of β-catenin and related osteogenic and osteoclastic factors after using miR-26b mimics and inhibitors in vivo. Moreover, BMSCs were treated with the β-catenin blocker Wnt-C59 and then transfected with miR-26b mimics or inhibitors. Then, we examined the expression of β-catenin as the direct target of miR-26b. The results of the present study indicate that miR-26b may modulate subchondral bone loss induced by abnormal occlusion and influence the osteogenic differentiation of subchondral BMSCs through β-catenin in the context of TMJ-OA progression.

Fluoride exposure duringintrauterine and lactation periods promotes changes in the offspring rats' alveolar bone

The importance of fluoride (F) for oral health is well established in the literature. However, evidence suggests that excessive exposure to this mineral is associated with adverse effects at different life stages and may affect many biological systems, especially mineralized tissues. The purpose of this study was to investigate the effects of F exposure during pregnancy and breastfeeding on the alveolar bone of the offspring since the alveolar bone is one of the supporting components of the dental elements. For this, the progeny rats were divided into three groups: control, 10 mg F/L, and 50 mg F/L for 42 (gestational and lactation periods). Analysis of the quantification of F levels in the alveolar bone by particle-induced gamma emission; Raman spectroscopy to investigate the physicochemical aspects and mineral components; computed microtomography to evaluate the alveolar bone microstructure and analyses were performed to evaluate osteocyte density and collagen quantification using polarized light microscopy. The results showed an increase in F levels in the alveolar bone, promoted changes in the chemical components in the bone of the 50 mg F/L animals (p < 0.001), and had repercussions on the microstructure of the alveolar bone, evidenced in the 10 mg F/L and 50 mg F/L groups (p < 0.001). Furthermore, F was able to modulate the content of organic bone matrix, mainly collagen; thus, this damage possibly reduced the amount of bone tissue and consequently increased the root exposure area of the exposed groups in comparison to a control group (p < 0.001). Our findings reveal that Fcan modulate the physicochemical and microstructural dimensions and reduction of alveolar bone height, increasing the exposed root region of the offspring during the prenatal and postnatal period. These findings suggest that F can modulate alveolar bone mechanical strength and force dissipation functionality.

A Comparative Evaluation of the Strain Transmitted through Prostheses on Implants with Two Different Macro-Structures and Connection during Insertion and Loading Phase: An In Vitro Study.

Background: The purpose of this study was to measure and compare the strain levels in the peri-implant bone as generated by the blade-like implant (BLI) and the screw-type implant (STI) with two different internal connections (hexagonal and conical) and with a 1:1 and 2:1 crown/implant (C/I) ratio. Methods: The implants (BLI and STI) were placed into sawbones according to the manufacturer’s protocol. Two strain gauges, horizontal and vertical to the implant axis, were placed around each implant on the bone surface 1 mm from the cervical part. Each implant was loaded by a material testing machine at a force of 100 N. Micro-strains (με) generated in the surrounding bone were measured by a strain gauge and recorded. Results: Recorded micro-strains were not significant in both the insertion and loading phases (p < 0.0625). The average recorded micro-strain values were lower in the horizontal dimension of STI with hexagonal connection when the C/I ratio was 2:1 compared with BLI, 210 με and 443 με, respectively. Conclusion: Within the limitations of this study, implant design, implant-abutment connection and C/I ratio did not influence strain values in bone and there is no statistically significant effect of these parameters on bone.

Biomechanical Evaluation of Stress Distribution in Equicrestal and Sub-crestally Placed, Platform-Switched Morse Taper Dental Implants in D3 Bone: Finite Element Analysis.

AimThe aim of the study was to assess the effect of implant placement depth on stress distribution in bone around a platform-switched and Morse taper dental implants placed at the equi-crestal and 1 mm and 2 mm sub-crestal levels in a D3 bone using the 3D finite element analysis.MethodologyA mechanical model of a partially edentulous maxilla was generated from a computerized tomography (CT) scan of an edentulous patient, as it can give exact bony contours of cortical bone. Also, from accurate geometric measurements obtained from the manufacturer, 3D models of Morse taper and platform-switched implants were manually drawn. The implant and bone models were then superimposed to simulate implant insertion in bone. Three implant positioning levels such as the equi-crestal, 1 mm sub-crestal, and 2 mm sub-crestal models were created, and meshing was done to create the number of elements for distribution of applying loads. The elastic properties of cortical bone and implant, such as Young's modulus and Poisson's ratio (µ), were determined. A load (axial and oblique) of 200N that simulated masticatory force was applied.ResultsOn comparing stresses within the bone around the equi-crestal and 1 mm and 2 mm sub-crestal implants, it was observed that the maximum stresses were seen within cortical bone around the equi-crestally placed implant (21.694), the least in the 2 mm sub-crestally placed implant (18.85), and intermediate stresses were seen within the 1 mm sub-crestally placed implant (18.876).ConclusionSub-crestal (1-2mm) placement of a Morse taper and a platform-switched implant is recommended for long-term success, as maximum von Mises stresses were found within cortical bone around the equi-crestal implant followed by the 1 mm sub-crestal implant and then the 2 mm sub-crestal implant.

A new perspective on the function of Tissue Non-Specific Alkaline Phosphatase: from bone mineralization to intra-cellular lipid accumulation.

Tissue-nonspecific alkaline phosphatase (TNAP) is one of four isozymes, which include germ cell, placental and intestinal alkaline phosphatases. The TNAP isozyme has 3 isoforms (liver, bone and kidney) which differ by tissue expression and glycosylation pattern. Despite a long history of investigation, the exact function of TNAP in many tissues is largely unknown. Only the bone isoform has been well characterised during mineralization where the enzyme hydrolyses pyrophosphate to inorganic phosphate, which combines with calcium to form hydroxyapatite crystals deposited as new bone. The inorganic phosphate also increases gene expression of proteins that support tissue mineralization. Recent studies have shown that TNAP is expressed in preadipocytes from several species, and that inhibition of TNAP activity causes attenuation of intracellular lipid accumulation in these and other lipid-storing cells. The mechanism by which TNAP stimulates lipid accumulation is not known; however, proteins that are important for controlling phosphate levels in bone are also expressed in adipocytes. This review examines the evidence that inorganic phosphate generated by TNAP promotes transcription that enhances the expression of the regulators of lipid storage and consequently, that TNAP has a major function of lipid metabolism.

Study of Alveolar Bone Remodeling Using Deciduous Tooth Stem Cells and Hydroxyapatite by Vascular Endothelial Growth Factor Enhancement and Inhibition of Matrix Metalloproteinase-8 Expression in vivo.

BackgroundPeriodontitis progression is characterized by alveolar bone loss, and its prevention is a major clinical problem in periodontal disease management. Matrix metalloproteinase-8 (MMP-8) has been shown to adequately monitor the treatment of chronic periodontitis patients as gingival crevicular fluid MMP-8s were positively associated with the severity of periodontal disease. Moreover, modulating the vascular endothelial growth factor (VEGF) levels in bones could be a good way to improve bone regeneration and cure periodontitis as VEGF promotes endothelial cell proliferation, proteolytic enzyme release, chemotaxis, and migration; all of which are required for angiogenesis.PurposeThe aim of this study was to determine the effect of hydroxyapatite incorporated with stem cells from exfoliated deciduous teeth (SHED) in Wistar rats’ initial alveolar bone remodeling based on the findings of MMP-8 and VEGF expressions.MethodsA hydroxyapatite scaffold (HAS) in conjunction with SHED was transplanted into animal models with alveolar mandibular defects. A total of 10 Wistar rats (Rattus norvegicus) were divided into two groups: HAS and HAS + SHED. Immunohistochemistry staining was performed after 7 days to facilitate the examination of MMP-8 and VEGF expressions.ResultsThe independent t-test found significant downregulation of MMP-8 and upregulation VEGF expressions in groups transplanted with HAS in conjunction with SHED compared with the HAS group (p < 0.05).ConclusionThe combination of SHED with HAS on alveolar bone defects may contribute to initial alveolar bone remodeling as evident through the assessments of MMP-8 and VEGF expressions.

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol.

The discovery that osteocytes secrete phosphaturic fibroblast growth factor 23 (FGF23) has defined bone as an endocrine organ. However, the autocrine and paracrine functions of FGF23 are still unknown. The present study focuses on the cellular and molecular mechanisms involved in the complex control of FGF23 production and local bone remodeling functions. FGF23 was assayed using ELISA kit in the presence or absence of 17β–estradiol in starved MLO-Y4 osteocytes. In these cells, a relationship between oxidative stress-induced apoptosis and up-regulation of active FGF23 levels due to MAP Kinases activation with involvement of the transcriptional factor (NF-kB) has been demonstrated. The active FGF23 increase can be due to up-regulation of its expression and post-transcriptional modifications. 17β–estradiol prevents the increase of FGF23 by inhibiting JNK and NF-kB activation, osteocyte apoptosis and by the down-regulation of osteoclastogenic factors, such as sclerostin. No alteration in the levels of dentin matrix protein 1, a FGF23 negative regulator, has been determined. The results of this study identify biological targets on which drugs and estrogen may act to control active FGF23 levels in oxidative stress-related bone and non-bone inflammatory diseases.

Effects of Sub-chronic Lead Exposure on Essential Element Levels in Mice.

Lead (Pb), a corrosion-resistant heavy non-ferrous metal, is one of the most common environmental neurotoxic metals. The effects of Pb on other essential metal elements are contradictory. Therefore, this in vivo study addressed the effects of sub-chronic Pb exposure on the distribution of other divalent metals, exploring the relationships between Pb levels in blood, teeth, bones, hair, and brain tissues. Thirty-two healthy male C57BL/6 mice received intragastric administration (i.g.) with 0, 12.5, 25, and 50mg/kg Pb acetate, once a day for 8weeks. Levels of Pb and other metal elements [including iron(Fe), zinc (Zn), magnesium (Mg), copper (Cu), and calcium(Ca)] in the whole blood, teeth, the right thighbone, hair, and brain tissues (including cortex, hippocampus, striatum, and hypothalamus) were detected with inductively coupled plasma-mass spectrometry (ICP-MS). Pb levels in all detectedorgans were increased after Pb-exposed for 8weeks. The results of relationship analysis between Pb levels in the tissues and lifetime cumulative Pb exposure (LCPE) showed that Pb levels in the blood, bone, and hair couldindirectly reflect the Pb accumulation in the murine brain. These measures might serve as valuable biomarkers for chronic Pb exposure reflective of the accumulation of Pb in the central nervous system (CNS). Sub-chronic Pb exposure for 8weeks altered Ca, Cu, Fe, and Zn levels, but no effects were noted on Mg levels in any of the analyzed tissues. Pb decreased Ca in teeth, Cu in thighbone and teeth, Zn in whole blood and hair, and Fe in hair. In contrast, Pb increased Ca levels in corpus striatum and hypothalamus, Cu levels in striatum, Zn levels in teeth, and Fe levels in hippocampus, thighbone, and teeth. The Pb-induced changes in metal ratios in various tissues may serve as valuable biomarkers for chronic Pb exposure as they are closely related to the accumulations of Pb in the murine CNS. The results suggest that altered distribution of several essential metal elements may be involved in Pb-induced neurotoxicity. Additional studies should address the interaction between Pb and essential metal elements in the CNS and other organs.