Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.532
Filtrar
1.
Food Chem ; 302: 125199, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400699

RESUMO

Animal bones are a high-quality source of protein and comprehensive nutrients and improper handling can cause resource wasting and environmental issues. Pretreatment before enzymatic hydrolysis of bone could significantly improve the enzymolytic efficiency, which is an essential step to achieve high value-added utilization of bones. This study investigated the effect of lipase pretreatment on the enzymatic hydrolysis of bones. The degree of hydrolysis after lipase pretreatment was 12.58%, which was 8.19% higher than that without pretreatment. Lipase pretreatment was optimal at 9% substrate concentration and initial pH 7.5, with 0.08% lipase, followed by 4 h incubation at 40 °C. Mechanism analysis indicated that lipase pretreatment improved the enzymolytic efficiency by significantly decreasing the lipid content, and changing the surface structure and surface element content of C, N, and O, promoting the attachment of alkaline protease onto the sample. Overall, lipase pretreatment was an effective method to reduce the costs of production.


Assuntos
Osso e Ossos/metabolismo , Lipase/metabolismo , Proteínas/metabolismo , Animais , Bovinos , Hidrólise
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1045-1051, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640962

RESUMO

OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) via a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; n=6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of ß-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice (P < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice (P < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of ß-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS: Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea , Osso e Ossos/metabolismo , Osteoclastos/efeitos dos fármacos , Ovariectomia , Teriparatida/administração & dosagem , Animais , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Feminino , Lâmina de Crescimento/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Ligante RANK/metabolismo , Teriparatida/farmacologia , beta Catenina/metabolismo
3.
Stomatologiia (Mosk) ; 98(4): 56-59, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31513151

RESUMO

The aim of the study was to determine the activity of alkaline phosphatase (AP), tartrate-resistant acid phosphatase (TRAP) and osteocalcin in oral fluid (OF) in patients with dental implants. Dental intraosseous implantation was performed in 164 patients, aged 45 to 60 years (mean age 54.6±4.17 years), 78 (47.6%) males and 86 (52.4%) females. In 75.6% of patients more than 3 teeth were absent. A total of 641 screw intraosseous implants of the MIS system were installed. Studies were performed prior to implant placement, at 7, 14, 21 days and 3 and 6 months. The control group consisted of 20 volunteers of comparable age, 9 (45.0%) males and 11 (55.0%) females. An increased activity of AP and TPAP was revealed, but the activity change of AP in comparison with the control group was not statistically significant. Activity of TRAP in patients before implantation was higher than in controls by 40.5% (p<0.05) in group without complications and by 61.9% (p<0.05) in patients with mucositis. After implantation, the activity of TPAP remained elevated for 6 months, the maximum activity was observed after 14 days and was 3 times higher than at baseline (p<0.01). The amount of osteocalcin increased, especially in the complicated course after the implantation. The highest values of osteocalcin were observed 14 days after implantation. Determination of the activity of TPAP in the OF after implantation can be used as an indicator of the state of bone metabolism.


Assuntos
Perda do Osso Alveolar , Osso e Ossos , Implantes Dentários , Osso e Ossos/metabolismo , Implantação Dentária , Implantação Dentária Endo-Óssea , Falha de Restauração Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
APMIS ; 127(12): 779-788, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31515843

RESUMO

Cefuroxime is widely used as antibiotic prophylaxis for orthopaedic procedures. We evaluated bone, subcutaneous tissue (SCT) and plasma pharmacokinetics of cefuroxime in male patients undergoing total knee replacement (TKR) after both traditional short-term infusion (STI) and continuous infusion (CI). Eighteen male patients undergoing TKR were randomly assigned to STI or CI of 1.5 g of cefuroxime. Measurements were obtained in plasma, SCT, cancellous and cortical bone every 30 min for 8 h following surgery. For sampling in solid tissues, microdialysis was applied. Population pharmacokinetic modelling was performed in order to estimate pharmacokinetic parameters, and to assess the probability of attaining cefuroxime concentrations above clinically relevant minimal inhibitory concentrations (MICs) for 65% and 90% of the 8 h dosing interval. Low SCT and cortical bone penetration were found in both the STI and the CI group, but the findings were only significant in the STI group. Irrespective of MIC, tissue and target, CI leads to improved probability of attaining relevant pharmacokinetic targets compared with STI. For the Staphylococcus aureus MIC breakpoint (4 µg/mL), STI leads to inadequate probability of target attainment. CI of 1.5 g of cefuroxime leads to improved probability of attaining relevant pharmacokinetic targets in male TKR patients compared with traditional STI. These findings suggest that application of CI may improve antibiotic prophylaxis for male TKR patients.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibioticoprofilaxia/métodos , Artroplastia do Joelho , Cefuroxima/administração & dosagem , Cefuroxima/farmacocinética , Infecções Relacionadas à Prótese/prevenção & controle , Idoso , Antibacterianos/sangue , Osso e Ossos/metabolismo , Cefuroxima/sangue , Esquema de Medicação , Humanos , Infusões Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Microdiálise , Pessoa de Meia-Idade , Tela Subcutânea/metabolismo
5.
Medicine (Baltimore) ; 98(32): e16770, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393399

RESUMO

BACKGROUND: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. PATIENTS AND METHODS: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I-IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1-L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were ETHICS AND DISSEMINATION:: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.


Assuntos
Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Denosumab/administração & dosagem , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Adulto , Inibidores da Aromatase/uso terapêutico , Biomarcadores , Osso e Ossos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos de Pesquisa
6.
J Clin Pathol ; 72(11): 741-747, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31467040

RESUMO

Phosphate in both inorganic and organic form is essential for several functions in the body. Plasma phosphate level is maintained by a complex interaction between intestinal absorption, renal tubular reabsorption, and the transcellular movement of phosphate between intracellular fluid and bone storage pools. This homeostasis is regulated by several hormones, principally the parathyroid hormone, 1,25-dihydroxyvitamin D and fibroblast growth factor 23. Abnormalities in phosphate regulation can lead to serious and fatal complications. In this review phosphate homeostasis and the aetiology, pathophysiology, clinical features, investigation and management of hypophosphataemia and hyperphosphataemia will be discussed.


Assuntos
Osso e Ossos/metabolismo , Hiperfosfatemia/sangue , Hipofosfatemia/sangue , Absorção Intestinal , Fosfatos/sangue , Reabsorção Renal , Animais , Biomarcadores/sangue , Osso e Ossos/fisiopatologia , Fatores de Crescimento de Fibroblastos/sangue , Homeostase , Humanos , Hiperfosfatemia/diagnóstico , Hiperfosfatemia/fisiopatologia , Hiperfosfatemia/terapia , Hipofosfatemia/diagnóstico , Hipofosfatemia/fisiopatologia , Hipofosfatemia/terapia , Hormônio Paratireóideo/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
7.
J Agric Food Chem ; 67(39): 10832-10843, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31464433

RESUMO

Excessive fluoride mainly causes skeletal lesions. Recently, it has been reported that an appropriate level of calcium can alleviate fluorosis. However, the appropriate concentration and mechanism of calcium addition is unclear. Hence, we evaluated the histopathology and ultrastructure, DNA fragmentation, hormonal imbalances, biomechanical levels, and expression of apoptosis-related genes after treating the rats with 150 mg/L NaF and different concentrations of CaCO3. Our results suggested that NaF induced the histopathological and ultrastructural injury, with a concomitant increase in the DNA fragmentation (P < 0.05) and serum OC (17.5 ± 0.89 pmoL/L) at 120 days. In addition, the qRT-PCR and western blotting results indicated that NaF exposure upregulated the mRNA and protein expression of Bax, Calpain, Caspase 12, Caspase 9, Caspase 7, Caspase 3, CAD, PARP, and AIF while downregulated Bcl-2 (P < 0.01) and decreased the bone ultimate load by 27.1%, the ultimate stress by 10.1%, and the ultimate deformity by 23.3% at 120 days. However, 1% CaCO3 supplementation decreased the serum OC (14.7 ± 0.65 pmoL/L), bone F content (P < 0.01), and fracture and breakage of collagen fibers and changed the expression of endoplasmic reticulum pathway-related genes and proteins at 120 days. Further, 1% CaCO3 supplementation increased the bone ultimate load by 20.9%, the ultimate stress by 4.89%, and the ultimate deformity by 21.6%. In summary, we conclude that 1% CaCO3 supplementation alleviated fluoride-induced bone damage by inhibiting endoplasmic reticulum stress and mitochondrial dysfunction.


Assuntos
Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fluoretos/toxicidade , Mitocôndrias/efeitos dos fármacos , Animais , Osso e Ossos/metabolismo , Caspases/genética , Caspases/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley
8.
Oncology ; 97(4): 236-244, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412345

RESUMO

INTRODUCTION: On a global scale, the malignant growth of mammary gland is the most common type of cancer in women. In the progress of mammary carcinoma, osseous metastatic invasion has a pivotal significance because it is a frequent complication occurring at an early stage of the disease. BACKGROUND: Bone metastases in breast cancer patients lead to increased mortality and decreased health-related quality of life. Therefore, early diagnostic assessment and treatment is requested. Meanwhile the progress of the disease should be monitored closely. Regarding health-related quality of life and lifetime prolongation, osseous metastases should be early diagnosed, therapied, and monitored. Up to date the gold standard is the whole-body scintigraphy. This kind of bone imaging features has high sensitivity but shows loss of specificity. AIM: This study aims to investigate the diagnostic versatility of bone markers in its resorption and formation function to detect bone metastases in patients with breast cancer. PATIENTS, MATERIALS, AND METHODS: For this purpose, the concentration of competing bone processing tumor markers in serums of 78 patients was detected and analyzed. Two groups of women with mammary carcinoma with and without osseous metastases were built to examine the presence (or absence) of statistically significant disparity of tumor marker concentration. The tumor markers employed in this study were the carboxyterminal collagen type I telopeptid (CTX), known as beta-crosslaps (ß-CTx), the alkaline phosphatase (AP), and its isoenzymes (especially the bone-specific AP [B-AP]). Additionally, the tumor markers for breast cancer (CA 15-3 and CEA) were analyzed in both groups. RESULTS: Our results provide evidence that in both groups, tumor markers such as ß-CTx and B-AP were a promising tool for the detection and exclusion of bone metastases in breast cancer. This comprehensive investigation shows both ß-CTx and B-AP are able to fulfill the conditions of a competent appliance to detect osseous metastases of patients with mammary carcinoma. CONCLUSION: Concerning the urgency of early and frequent detection, staging, and disease monitoring of mammary carcinoma with osseous metastases, this study renewed and underlined the importance of biochemical tumor markers - especially ß-CTx and B-AP - and laid a clinical-based cornerstone to build up on a prospective research.


Assuntos
Biomarcadores/metabolismo , Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Neoplasias da Mama/metabolismo , Fosfatase Alcalina/metabolismo , Biomarcadores Tumorais , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Colágeno Tipo I/metabolismo , Feminino , Humanos , Mucina-1/metabolismo , Metástase Neoplásica , Qualidade de Vida , Curva ROC , Cintilografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Imagem Corporal Total
9.
Nat Commun ; 10(1): 2958, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273195

RESUMO

RNAi-based bone anabolic gene therapy has demonstrated initial success, but many practical challenges are still unmet. Here, we demonstrate that a recombinant adeno-associated virus 9 (rAAV9) is highly effective for transducing osteoblast lineage cells in the bone. The adaptor protein Schnurri-3 (SHN3) is a promising therapeutic target for osteoporosis, as deletion of shn3 prevents bone loss in osteoporotic mice and short-term inhibition of shn3 in adult mice increases bone mass. Accordingly, systemic and direct joint administration of an rAAV9 vector carrying an artificial-microRNA that targets shn3 (rAAV9-amiR-shn3) in mice markedly enhanced bone formation via augmented osteoblast activity. Additionally, systemic delivery of rAAV9-amiR-shn3 in osteoporotic mice counteracted bone loss and enhanced bone mechanical properties. Finally, we rationally designed a capsid that exhibits improved specificity to bone by grafting the bone-targeting peptide motif (AspSerSer)6 onto the AAV9-VP2 capsid protein. Collectively, our results identify a bone-targeting rAAV-mediated gene therapy for osteoporosis.


Assuntos
Reabsorção Óssea/complicações , Reabsorção Óssea/prevenção & controle , Osso e Ossos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dependovirus/metabolismo , Inativação Gênica , Osteoporose/complicações , Animais , Reabsorção Óssea/patologia , Osso e Ossos/virologia , Capsídeo/metabolismo , Cartilagem/virologia , Modelos Animais de Doenças , Deleção de Genes , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Sorogrupo
10.
J Photochem Photobiol B ; 197: 111515, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31255939

RESUMO

An extraordinary arrangement of research is as yet going on in the area of orthopedic implants advancement to determine different issues being looked by the engineering today. In spite of a few detriments of the orthopedic metallic inserts, they keep on being utilized, essentially as a result of their unrivaled mechanical properties. We investigated the conceivable utilization of silicon carbide (SiC) as a nano-ceramic covering material of titanium (Ti)-based all out femoral substitution implants. The thought is to keep wear garbage arrangement from the delicate titanium exterior. Silicon carbide is a hard and firmly holding bio-ceramic surface substance, and in light of these physico-chemical properties, it isn't actually degradable, just like the case with apatite (HA). To improve cytocompatibility and osseous-integration, we deposited anodized titanium nanotubes (TiO2) inserts, by electrochemical deposition method (EDM), with silicon carbide (SiC) with apatite (SiC@HA). The deposition was affirmed by SEM, while phase composition properties were assessed by XRD. Calcium affidavit, osteocalcin creation, and articulation of bone genes were essentially higher in rodent osteoblast cell culture on SiC@HA-covered anodized titanium nanotubes than in cells cultured on uncoated anodized titanium nanotubes. Implantation into rodent femurs likewise demonstrated that the SiC@HA-covered substance had unrivaled osseous-integration movement in correlation with that of customary inserts, as evaluated by in vivo tomography and histology. Therefore, anodized titanium nanotubes covered with SiC@HA holds guarantee as an orthopedic implant substance.


Assuntos
Regeneração Óssea , Compostos Inorgânicos de Carbono/química , Materiais Revestidos Biocompatíveis/química , Durapatita/química , Nanopartículas/química , Compostos de Silício/química , Titânio/química , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Adesão Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fraturas do Fêmur/terapia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteocalcina/metabolismo , Próteses e Implantes , Ratos
11.
Nat Commun ; 10(1): 2570, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239437

RESUMO

Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.


Assuntos
Osso e Ossos/química , Quelantes/administração & dosagem , Piridonas/administração & dosagem , Lesões por Radiação/terapia , Urânio/toxicidade , Adsorção , Animais , Osso e Ossos/metabolismo , Quelantes/química , Feminino , Humanos , Rim/química , Rim/metabolismo , Ligantes , Camundongos , Piridonas/química , Lesões por Radiação/induzido quimicamente , Lesões por Radiação/metabolismo , Urânio/química , Urânio/metabolismo
12.
Nat Commun ; 10(1): 2829, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249296

RESUMO

Extracellular vesicles (EVs) are involved in the regulation of cell physiological activity and the reconstruction of extracellular environment. Matrix vesicles (MVs) are a type of EVs released by bone-related functional cells, and they participate in the regulation of cell mineralization. Here, we report bioinspired MVs embedded with black phosphorus (BP) and functionalized with cell-specific aptamer (denoted as Apt-bioinspired MVs) for stimulating biomineralization. The aptamer can direct bioinspired MVs to targeted cells, and the increasing concentration of inorganic phosphate originating from BP can facilitate cell biomineralization. The photothermal effect of the Apt-bioinspired MVs can also promote the biomineralization process by stimulating the upregulated expression of heat shock proteins and alkaline phosphatase. In addition, the Apt-bioinspired MVs display outstanding bone regeneration performance. Our strategy provides a method for designing bionic tools to study the mechanisms of biological processes and advance the development of medical engineering.


Assuntos
Vesículas Extracelulares/metabolismo , Fósforo/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/metabolismo , Biomineralização , Osso e Ossos/química , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Vesículas Extracelulares/química , Feminino , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/química , Osteoblastos/metabolismo , Fosfatos/metabolismo , Fósforo/química , Ratos
13.
J Food Sci ; 84(7): 1909-1919, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31237973

RESUMO

Osteoporosis is a common metabolic bone disease that is often seen in bedridden patients and astronauts. Long-term bed rest and nonweight bearing tend to induce disuse osteoporosis. Calcium supplements are commonly used to help treat disuse osteoporosis along with medications, most of which are calcium carbonate based, but they have poor absorption effects. In this study, we prepared a novel Auricularia auricula peptide-calcium complex (AP-Ca) and evaluated its protective effects on disuse osteoporosis. In vitro assays showed that AP-Ca significantly increased the contents of calcium (P < 0.05) and the activity of alkaline phosphatase (AKP; P < 0.05) of osteoblasts cultured in a two-dimensional-rotating wall vessel. Meanwhile, supplementation with AP-Ca also inhibited the production of pro-inflammatory factors induced by the loss of stress, especially TNF-α (P < 0.05). In vivo, a mouse tail suspension (TS) model was established, and the results showed that AP-Ca helped to improve bone mineral density, bone mineral content, and bone organic content in TS mice and effectively alleviated the alteration of enzymes related to bone metabolism, including AKP (P < 0.05) and serum tartrate-resistant acid phosphatase (P < 0.05), to avoid more serious bone loss induced by TS. Furthermore, we found that AP-Ca downregulated the bone resorption-associated pro-inflammatory genes interleukin-1 (IL-1), tumor necrosis factor-α, and IL-6 by 59.53 ± 3.55%, 48.01 ± 5.68%, and 40.00 ± 5.89%, respectively (P < 0.05). In conclusion, AP-Ca showed potential to suppress bone loss induced by disuse and might be considered a new alternative to reduce the risk of disuse osteoporosis. PRACTICAL APPLICATION: This peptide-calcium complex supplement exhibited protective effects on the bone loss induced by disuse, which provided a new alternative for patients and astronauts to reduce the risk of disuse osteoporosis.


Assuntos
Basidiomycota/química , Cálcio/metabolismo , Proteínas Fúngicas/química , Osteoporose/tratamento farmacológico , Peptídeos/administração & dosagem , Hidrolisados de Proteína/química , Fosfatase Alcalina/sangue , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/química , Osso e Ossos/metabolismo , Humanos , Masculino , Camundongos , Osteoporose/fisiopatologia , Peptídeos/química , Hidrolisados de Proteína/farmacologia , Transdução de Sinais/efeitos dos fármacos
14.
J Dairy Sci ; 102(8): 7608-7617, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202659

RESUMO

Exploring the relationship between nutrition, skeletal development, and aging is important in maintaining bone health. Even further, understanding the complexity of skeletal homeostasis may assist in reducing the prevalence of skeletal disease, especially osteoporosis. The skeleton is unique in that it can adapt to various physical pressures, maintain shape, and remodel itself to increase integrity and strength. For decades, it was thought that increasing skeletal health was as simple as drinking three 8-oz. glasses of milk per day due to high levels of bioavailable calcium. New research into the bioactive components of milk have revealed other roles in promoting skeletal health. Milk contains various bioactive peptides, houses genetic information in milk-derived exosomes, and supplies relevant amounts of nutrients important for bone health. In this review, we discuss the basics of skeletal formation and homeostasis, dive into the potential effects of milk on the growing skeleton, and present contrasting findings.


Assuntos
Desenvolvimento Ósseo , Osso e Ossos/metabolismo , Leite/metabolismo , Animais , Humanos , Leite/química , Valor Nutritivo
15.
Life Sci ; 231: 116556, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31194990

RESUMO

Triiodothyronine (T3) and estrogen (E2) play important roles in the bone remodeling process and signaling of receptor activator of the nuclear factor-kappa ß (RANKL) and osteoprotegerin (OPG) expressed by osteoblasts. However, little is known of the molecular action of these hormones in conditions of hyperthyroidism and associated E2 in human cells. AIMS: This study evaluated the effects of the physiological concentration of E2 (10 nM), alone or in association with physiological (1 nM) and supraphysiological (10 nM) concentrations of T3, on RANKL and OPG gene expression in human osteoblasts. MAIN METHODS: Alkaline phosphatase and osteocalcin assays were performed to verify the presence of mature osteoblasts. After mimicking the experimental hyperthyroidism in osteoblasts untreated or treated with E2, RANKL and OPG gene expression was analyzed by real-time PCR and protein expression by western Blot and ELISA. Alizarin Red staining analyzed the amount of bone matrix after hormonal treatments. KEY FINDINGS: E2 enhanced the gene expression of OPG when associated with 1 nM and 10 nM T3. E2 was able to restore the bone matrix after an initial decrease using 1 nM and 10 nM T3. The protective effect of E2 on the RANKL and OPG signaling pathway was demonstrated. E2 restored the bone matrix induced by experimental hyperthyroidism. SIGNIFICANCE: The data highlight the importance of E2 to maintain OPG expression and osteoblast activity against possible loss of bone mass, especially in conditions where T3 is in excess.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Estrogênios/fisiologia , Osteoblastos/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Remodelação Óssea/fisiologia , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Estrogênios/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertireoidismo/metabolismo , Células-Tronco Mesenquimais/fisiologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Tri-Iodotironina/metabolismo , Tri-Iodotironina/fisiologia
16.
Int J Mol Sci ; 20(9)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058825

RESUMO

Mg-based alloys have great potential for development into fixation implants because of their highly biocompatible and biodegradable metallic properties. In this study, we sought to determine the biocompatibility of Mg60Zn35Ca5 bulk metallic glass composite (BMGC) with fabricated implants in a rabbit tendon-bone interference fixation model. We investigated the cellular cytotoxicity of Mg60Zn35Ca5 BMGC toward rabbit osteoblasts and compared it with conventional titanium alloy (Ti6Al4V) and polylactic acid (PLA). The results show that Mg60Zn35Ca5 BMGC may be classed as slightly toxic on the basis of the standard ISO 10993-5. We further characterized the osteogenic effect of the Mg60Zn35Ca5 BMGC extraction medium on rabbit osteoblasts by quantifying extracellular calcium and mineral deposition, as well as cellular alkaline phosphatase activity. The results of these tests were found to be promising. The chemotactic effect of the Mg60Zn35Ca5 BMGC extraction medium on rabbit osteoblasts was demonstrated through a transwell migration assay. For the in vivo section of this study, a rabbit tendon-bone interference fixation model was established to determine the biocompatibility and osteogenic potential of Mg60Zn35Ca5 BMGC in a created bony tunnel for a period of up to 24 weeks. The results show that Mg60Zn35Ca5 BMGC induced considerable new bone formation at the implant site in comparison with conventional titanium alloy after 24 weeks of implantation. In conclusion, this study revealed that Mg60Zn35Ca5 BMGC demonstrated adequate biocompatibility and exhibited significant osteogenic potential both in vitro and in vivo. These advantages may be clinically beneficial to the development of Mg60Zn35Ca5 BMGC implants for future applications.


Assuntos
Materiais Biocompatíveis/química , Cálcio/química , Vidro/química , Magnésio/química , Nanopartículas Metálicas/química , Osteogênese/efeitos dos fármacos , Zinco/química , Animais , Materiais Biocompatíveis/farmacologia , Biomarcadores , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Movimento Celular , Sobrevivência Celular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Imagem Tridimensional , Teste de Materiais , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Coelhos , Tendões , Microtomografia por Raio-X
17.
Molecules ; 24(9)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035627

RESUMO

Nowadays, regenerative medicine has paid special attention to research (in vitro and in vivo) related to bone regeneration, specifically in the treatment of bone fractures or skeletal defects, which is rising worldwide and is continually demanding new developments in the use of stem cells, growth factors, membranes and scaffolds based on novel nanomaterials, and their applications in patients by using advanced tools from molecular biology and tissue engineering. Strontium (Sr) is an element that has been investigated in recent years for its participation in the process of remodeling and bone formation. Based on these antecedents, this is a review about the Strontium Folate (SrFO), a recently developed non-protein based bone-promoting agent with interest in medical and pharmaceutical fields due to its improved features in comparison to current therapies for bone diseases.


Assuntos
Regeneração Óssea , Ácido Fólico/metabolismo , Estrôncio/metabolismo , Tecidos Suporte , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Polpa Dentária/citologia , Ácido Fólico/química , Humanos , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Estrôncio/química , Engenharia Tecidual , Tecidos Suporte/química , Vitamina B 12/química , Vitamina B 12/metabolismo , Vitamina B 6/química , Vitamina B 6/metabolismo
18.
Life Sci ; 229: 261-276, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31082400

RESUMO

AIM: Myokines are associated with regulation of bone and muscle mass. However, limited information is available regarding the impact of myokines on glucocorticoid (GC) mediated adverse effects on the musculoskeletal system. This study investigates the role of myokine fibroblast growth factor-2 (FGF-2) in regulating GC-induced deleterious effects on bone and skeletal muscle. METHODS: Primary osteoblast cells and C2C12 myoblast cell line were treated with FGF-2 and then exposed to dexamethasone (GC). FGF-2 mediated attenuation of the inhibitory effect of GC on osteoblast and myoblast differentiation and muscle atrophy was assessed through quantitative PCR and western blot analysis. Further, FGF-2 was administered subcutaneously to dexamethasone treated mice to collect bone and skeletal muscle tissue for in vivo analysis of bone microarchitecture, mechanical strength, histomorphometry and for histological alterations in treated tissue samples. KEY FINDINGS: FGF-2 abrogated the dexamethasone induced inhibitory effect on osteoblast differentiation by modulating BMP-2 pathway and inhibiting Wnt antagonist sclerostin. Further, dexamethasone induced atrophy in C2C12 cells was mitigated by FGF-2 as evident from down regulation of atrogenes expression. FGF-2 prevented GC-induced impairment of mineral density, biomechanical strength, trabecular bone volume, cortical thickness and bone formation rate in mice. Additionally, skeletal muscle tissue from GC treated mice displayed weak myostatin immunostaining and reduced expression of atrogenes following FGF-2 treatment. SIGNIFICANCE: FGF-2 mitigated GC induced effects through inhibition of sclerostin and myostatin expression in bone and muscle respectively. Taken together, this study exhibited the role of exogenous FGF-2 in sustaining osteoblastogenesis and inhibiting muscle atrophy in presence of glucocorticoid.


Assuntos
Osso e Ossos/metabolismo , Dexametasona/toxicidade , Fator 2 de Crescimento de Fibroblastos/farmacologia , Glicoproteínas/antagonistas & inibidores , Músculo Esquelético/metabolismo , Doenças Musculoesqueléticas/tratamento farmacológico , Miostatina/antagonistas & inibidores , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Diferenciação Celular , Células Cultivadas , Glucocorticoides/toxicidade , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Doenças Musculoesqueléticas/induzido quimicamente , Doenças Musculoesqueléticas/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos
19.
Int J Infect Dis ; 85: 127-131, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096056

RESUMO

OBJECTIVES: Daptomycin has shown clinical efficacy in diabetic foot infections (DFI). However, only limited data are available on its bone penetration in this particular population. The aim of this study was to determine daptomycin bone concentrations in patients with DFI undergoing surgery after multiple daptomycin infusions and to determine bone daptomycin inhibitory quotients (IQs) for the predominant gram-positive species involved in DFI. METHODS: Fourteen adult patients hospitalized with DFI treated with daptomycin and requiring surgical bone debridement and amputation were included in this single-centre prospective study. Daptomycin concentrations in serum and bone were determined by HPLC at steady state. Bone IQs were then calculated according to different minimum inhibitory concentrations (MICs; range 0.25-4mg/l) that are representative of the main MICs for Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and Enterococcus sp populations. RESULTS: Residual and peak concentrations varied from 4.5mg/l to 39.9mg/l and from 31.8mg/l to 110.9mg/l, respectively. Bone daptomycin concentrations at the moment of surgery varied from 1.2mg/l to 17mg/l. Up to a MIC of 1mg/l, which is the epidemiological cut-off value (ECOFF) and breakpoint value for S. aureus and CoNS, all bone daptomycin IQs were positive. The highest bone IQs were observed with Staphylococcus species. Calculated bone IQs for Enterococcus species were often weak at MIC values near the ECOFF. CONCLUSIONS: Daptomycin penetrates bone well in patients treated for DFI. At an initially recommended dosage of 6mg/kg, bone concentrations are likely to be effective against staphylococcal infections and infections due to low-MIC Enterococcus.


Assuntos
Antibacterianos/farmacocinética , Osso e Ossos/metabolismo , Daptomicina/farmacocinética , Pé Diabético/complicações , Doenças do Pé/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Enterococcus/efeitos dos fármacos , Feminino , Doenças do Pé/complicações , Doenças do Pé/metabolismo , Doenças do Pé/cirurgia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Staphylococcus/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
20.
Adv Colloid Interface Sci ; 269: 219-235, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31096075

RESUMO

This article focuses on the relevance of amorphous calcium (and magnesium) phosphates in living organisms. Although crystalline calcium phosphate (CaP)-based materials are known to constitute the major inorganic constituents of human hard tissues, amorphous CaP-based structures, often in combination with magnesium, are frequently employed by Nature to build up components of our body and guarantee their proper functioning. After a brief description of amorphous calcium phosphate (ACP) formation mechanism and structure, this paper is focused on the stabilization strategies that can be used to enhance the lifetime of the poorly stable amorphous phase. The various locations of our body in which ACP (pure or in combination with Mg2+) can be found (i.e. bone, enamel, small intestine, calciprotein particles and casein micelles) are highlighted, showing how the amorphous nature of ACP is often of paramount importance for the achievement of a specific physiological function. The last section is devoted to ACP-based biomaterials, focusing on how these materials differ from their crystalline counterparts in terms of biological response.


Assuntos
Fosfatos de Cálcio/metabolismo , Materiais Dentários/química , Compostos de Magnésio/metabolismo , Fosfatos/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Osso e Ossos/química , Osso e Ossos/metabolismo , Fosfatos de Cálcio/análise , Fosfatos de Cálcio/química , Caseínas/química , Esmalte Dentário/química , Esmalte Dentário/metabolismo , Humanos , Intestino Delgado/química , Intestino Delgado/metabolismo , Micelas , Leite Humano/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA