Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23.590
Filtrar
1.
Braz. j. biol ; 84: e251970, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345559

RESUMO

Abstract In order to better understand the ossification processes in anurans our study was carried out on tadpoles and adults of Lithobates catesbeianus. In this sense, we characterized the kinetic properties of alkaline phosphatase with p-nitrophenylphosphatase (pNPP) and pyrophosphate (PPi) and evaluated the activities of tartrate-resistant acid phosphatase and acid phosphatase. The enzyme extracts were obtained from tadpoles and adult femurs, which were divided into epiphysis and diaphysis. After homogenization, the samples were submitted to differential centrifugation to obtain cell membranes and, further, to phospholipase C (PIPLC) treatment, to remove membrane-bound proteins anchored by phosphatidylinositol. The average of specific activity for pNPP hydrolysis (at pH 10.5) by alkaline phosphatase released by phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus cereus among different bone regions at different animal ages was 1,142.57 U.mg-1, while for PPi hydrolysis (at pH 8.0), it was 1,433.82 U.mg-1. Among the compounds tested for enzymatic activity, the one that influenced the most was EDTA, with approximately 67% of inhibition for pNPPase activity and 77% for PPase activity. In the case of kinetic parameters, the enzyme showed a "Michaelian" behavior for pNPP and PPi hydrolysis. The Km value was around 0.6mM for pNPPase activity and ranged from 0.01 to 0.11mM for PPase activity, indicating that the enzyme has a higher affinity for this substrate. The study of pNPP and PPi hydrolysis by the enzyme revealed that the optimum pH of actuation for pNPP was 10.5, while for PPi, which is considered the true substrate of alkaline phosphatase, was 8.0, close to the physiological value. The results show that regardless of the ossification type that occurs, the same enzyme or isoenzymes act on the different bone regions and different life stages of anurans. The similarity of the results of studies with other vertebrates shows that anurans can be considered excellent animal models for the study of biological calcification.


Resumo Para melhor compreender o processo de ossificação em anuros, nosso estudo foi conduzido em girinos e adultos de Lithobates catesbeianus. Nesse sentido, as propriedades cinéticas da fosfatase alcalina com p-nitrofenilfosfato (pNPP) e pirofosfato (PPi) foram caracterizadas, e as atividades enzimáticas das fosfatases ácida e ácida tartarato resistente foram avaliadas. Os extratos enzimáticos foram obtidos de fêmur de girinos e adultos, divididos em epífise e diáfise. Após a homogeneização as amostras foram submetidas à centrifugação diferencial para obter membrana celular e, em seguida, ao tratamento com fosfolipase C (PIPLC), para remover as proteínas de membrana ancoradas por fosfatidilinositol. A média da atividade específica da fosfatase alcalina, liberada pela PIPLC de Bacillus cereus, para a hidrólise de pNPP (pH 10,5) nas diferentes regiões do fêmur e idades dos animais foi de 1.142,57 U.mg-1, enquanto para a hidrólise do PPi (pH 8,0) foi de 1.433,82 U.mg-1. Entre os compostos testados para a atividade enzimática, o de maior influência foi o EDTA, inibindo aproximadamente 67% e 77% das atividades de pNPPase e PPase, respectivamente. Quanto aos parâmetros cinéticos, a enzima apresentou comportamento Michaeliano para a hidrólise dos dois substratos. O valor de Km foi de 0,6 mM para a atividade de pNPPase e variou de 0,01 a 0,11 para a atividade de PPase, indicando uma maior afinidade por esse substrato. O estudo da hidrólise de pNPP e PPi revelou que o pH ótimo aparente de atuação foi de 10,5 para o pNPP e 8,0 para o PPi, próximo ao fisiológico, sendo que esse é considerado o substrato natural da fosfatase alcalina. Os resultados demonstram que, apesar do tipo de ossificação que ocorre, a mesma enzima ou isoenzimas, atuam nos diferentes locais do osso e estágios de vida dos anuros. A similaridade dos estudos com os realizados com outros vertebrados apontam que os anuros podem ser considerados excelentes modelos animais para o estudo da calcificação biológica.


Assuntos
Animais , Osteogênese , Fosfatase Alcalina/metabolismo , Rana catesbeiana , Osso e Ossos/metabolismo , Cinética
2.
Methods Mol Biol ; 2582: 343-353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370362

RESUMO

Bone metastasis and bone destruction are common occurrences in human malignancies, including breast, prostate, and lung cancer, and are associated with a high morbidity rate because of intractable bone pain, pathological fractures, hypercalcemia, and nerve compression. Animal models of bone metastasis and bone destruction are important tools to investigate the pathogenesis and develop treatment strategies. However, there are few models of spontaneous bone metastasis despite the fact that animals often spontaneously develop cancer. Here, we describe methods for developing a mouse model of breast cancer bone metastasis achieved by injection of MDA-MB-231 breast cancer cells into the left cardiac ventricle. In addition, we introduce mouse model of the bone destruction by injection of SAS oral squamous cell carcinoma cells into the bone marrow space of the right tibial metaphysis. These assays can be applied to studies on roles of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) protein in tumor metastasis and development of treatment strategies targeting CCN proteins.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Carcinoma de Células Escamosas , Neoplasias Bucais , Camundongos , Masculino , Animais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Neoplasias Ósseas/patologia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Osso e Ossos/metabolismo , Proteínas , Modelos Animais de Doenças , Neoplasias da Mama/patologia , Linhagem Celular Tumoral
3.
Proc Natl Acad Sci U S A ; 119(48): e2209231119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36417434

RESUMO

The shaping of bone structures relies on various cell types and signaling pathways. Here, we use the zebrafish bifurcating fin rays during regeneration to investigate bone patterning. We found that the regenerating fin rays form via two mineralization fronts that undergo an osteoblast-dependent fusion/stitching until the branchpoint, and that bifurcation is not simply the splitting of one unit into two. We identified tartrate-resistant acid phosphatase-positive osteolytic tubular structures at the branchpoints, hereafter named osteolytic tubules (OLTs). Chemical inhibition of their bone-resorbing activity strongly impairs ray bifurcation, indicating that OLTs counteract the stitching process. Furthermore, by testing different osteoactive compounds, we show that the position of the branchpoint depends on the balance between bone mineralization and resorption activities. Overall, these findings provide a unique perspective on fin ray formation and bifurcation, and reveal a key role for OLTs in defining the proximo-distal position of the branchpoint.


Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Osteoblastos/metabolismo , Transdução de Sinais , Osso e Ossos/metabolismo
4.
Cells ; 11(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36359752

RESUMO

The culture of osteoblasts (OB) of human origin is a useful experimental model in studying bone biology, osteogenic differentiation, functions of bone proteins, oncological processes in bone tissue, testing drugs against bone desires, and many other fields. The purpose of the present study is to share a workflow that has established the conditions to efficiently isolate and grow OB cells obtained from surgically removed bones from human donors. The protocol described here also shows how to determine cell phenotype. Here we provide characteristics of cells isolated by this protocol that might help researchers to decide if such OB are suitable for the purposes of their study. Osteoblasts isolated from collagenase-treated explants of adult bones are able to proliferate and keep their phenotype in culture. OB cells have high synthetic properties. They express osteomarkers, such as RUNX2, osteocalcin, BMP2, and osteopontin both in control conditions and in an osteogenic medium that could be estimated by qPCR and immunocytochemical staining and by Western blotting. Induction of osteogenic differentiation does not dramatically influence the synthetic properties of OB cells, while the cells gain the ability to extracellular mineralization only in an osteogenic medium.


Assuntos
Osteoblastos , Osteogênese , Humanos , Osteogênese/genética , Osteoblastos/metabolismo , Diferenciação Celular , Osteocalcina/metabolismo , Osso e Ossos/metabolismo
5.
Arch Endocrinol Metab ; 66(5): 611-620, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36382750

RESUMO

Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual's development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues.


Assuntos
Osso e Ossos , Resistência à Insulina , Humanos , Osso e Ossos/metabolismo , Tecido Adiposo/metabolismo , Remodelação Óssea , Músculos/metabolismo , Metabolismo Energético
6.
Arch Endocrinol Metab ; 66(5): 756-764, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36382765

RESUMO

Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy.


Assuntos
Doenças Ósseas Metabólicas , Doença Celíaca , Fraturas Ósseas , Osteoporose , Humanos , Doença Celíaca/complicações , Dieta Livre de Glúten , Osso e Ossos/metabolismo , Densidade Óssea , Osteoporose/complicações , Doenças Ósseas Metabólicas/etiologia , Fraturas Ósseas/etiologia
7.
Int J Mol Sci ; 23(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36430239

RESUMO

Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.


Assuntos
Colágeno Tipo I , Cisteína Proteases , Catepsina K/metabolismo , Colágeno Tipo I/metabolismo , Osso e Ossos/metabolismo
8.
Curr Top Membr ; 89: 221-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210150

RESUMO

TRPV4 is a non-selective cation channel that belongs to the TRP super family. This channel can be activated by physiological temperatures and mechanical stimuli. In addition, TRPV4 is modulated by several endogenous mediators including specific lipids, cholesterol and their metabolic products. TRPV4 gene is present in all vertebrates and is widely expressed in tissues originating from ectoderm, endoderm and mesoderm. Although TRPV4 knockout is not lethal, point mutations in TRPV4 cause severe clinical phenotypes with variable penetration in human population. These mutations are mostly "gain-of-function" in nature and primarily affect muscles, bones and peripheral neurons, endorsing TRPV4 as critical regulator of musculoskeletal systems. Here we critically analyze the involvement of TRPV4 in musculoskeletal system. Studies of TRPV4 mutations provide detailed information on musculoskeletal disorders at molecular, cellular and metabolic levels.


Assuntos
Doenças Musculoesqueléticas , Canais de Cátion TRPV , Animais , Osso e Ossos/metabolismo , Colesterol , Humanos , Fenótipo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
9.
Genes (Basel) ; 13(10)2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36292748

RESUMO

To evaluate the prevention and treatment effect of a Chinese herbal formula (CHF) on the bone disease of Cobb broiler chickens, compare its efficacy with Bisphosphonates (BPs), and provide a theoretical basis for studying the nutritional regulation technology of CHF to improve the bone characteristics of broiler chickens. In this study, 560 one-day-old Cobb broiler chickens were examined for the influence of Chinese herbal formula (CHF) and Bisphosphonates (BPs). Different doses of CHF and BPs were added to the diet, and the 30- and 60-day-old live weight, tibial bone strength, the microstructure of the distal femur cancellous bone, blood biochemical indexes related to bone metabolism, and genes related to bone metabolism were determined and analyzed. The results showed that the live weight of Cobb broilers fed with CHF and BPs in the diet was as follows: The live weight of the CHF group was higher than that of the normal control (NC) group, while the live weight of the BPs group was lower than that of the NC group; the CHF and BPs improved the bone strength of Cobb broilers and increased the elastic modulus, yield strength, and maximum stress of the tibia. CHF and BPs increased the cancellous bone mineral density (BMD), bone tissue ratio (BV/TV), bone surface area tissue volume ratio (BS/TV), bone trabecular thickness (Tb.Th), and bone trabecular number (Tb.N) in the distal femur, and decreased the bone surface area bone volume ratio (BS/BV) and bone trabecular separation (Tb.Sp). Thus, the microstructure of the bone tissue of the distal femur was improved to a certain extent. Both the CHF and the BPs also increased the serum levels of the vitamin D receptor (VDR), osteoprotegerin (OPG), and alkaline phosphatase (ALP), and decreased the content of osteocalcin (OT). Meanwhile, CHF and BPs upregulated the expression of osteogenic genes (BMP-2, OPG, Runx-2) to promote bone formation and downregulated the expression of osteoclastic genes (RANK, RANKL, TNF-α) to inhibit bone resorption, thus affecting bone metabolism. Conclusion: The CHF could improve the skeletal characteristics of Cobb broilers by upregulating the expression of bone-forming-related genes and downregulating the expression of bone-breaking-related genes, thus preventing and controlling skeletal diseases in Cobb broilers. Its effect was comparable to that of BPs. Meanwhile, the CHF-H group achieved the best results in promoting the growth and improvement of the skeletal characteristics of Cobb broilers based on the live weight and skeletal-characteristics-related indexes.


Assuntos
Galinhas , Osteoprotegerina , Animais , Osteoprotegerina/genética , Galinhas/metabolismo , Receptores de Calcitriol/metabolismo , Osteocalcina , Fosfatase Alcalina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Osso e Ossos/metabolismo , Difosfonatos , China
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1130-1135, 2022 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-36305114

RESUMO

OBJECTIVES: To study the level of serum vitamin K2 (VitK2) and its association with bone metabolism markers osteocalcin (OC), type I procollagen amino-terminal peptide (PINP), and type I collagen carboxy-terminal peptide (CTX) in children. METHODS: A prospective analysis was performed on 1 732 children who underwent routine physical examination from October 2020 to October 2021. The serum levels of VitK2 and 25-hydroxy vitamin D [25(OH)D] were measured. According to age, they were divided into four groups: <1 year, 1-3 years group, >3-6 years group, and >6-14 years. A total of 309 children with 25(OH)D≥50 nmol/L were screened out, and serum levels of OC, PINP, and CTX were measured to investigate the correlation of the serum levels of OC, PINP, and CTX with serum VitK2 levels in different age groups. RESULTS: The prevalence rate of serum VitK2 deficiency was 52.31% (906/1 732). The VitK2 deficiency group had higher prevalence rates of overweight/obesity and growth pain (≥3 years of age) than the normal VitK2 group (P<0.05). There were differences in the prevalence rate of serum VitK2 deficiency (P<0.0083) and the serum level of VitK2 (P<0.05) between the 1-3 years group and the >6-14 years group. The <1 year group had a higher serum level of CTX and a lower serum level of PINP than the >3-6 years group and the >6-14 years group (P<0.05). The <1 year group had a lower serum level of OC than the >6-14 years group (P<0.05). Serum VitK2 level was positively correlated with OC level (rs=0.347, P<0.01), and CTX level was negatively correlated with PINP level (rs=-0.317, P<0.01). CONCLUSIONS: Serum VitK2 deficiency may be associated with overweight/obesity. Serum VitK2 may affect the level of OC and even bone health.


Assuntos
Osso e Ossos , Obesidade , Sobrepeso , Vitamina K , Criança , Humanos , Lactente , Biomarcadores/metabolismo , Colágeno Tipo I/metabolismo , Obesidade/complicações , Osteocalcina/metabolismo , Sobrepeso/complicações , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Vitamina K/sangue , Pré-Escolar , Adolescente , Osso e Ossos/metabolismo
11.
Front Endocrinol (Lausanne) ; 13: 989135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267573

RESUMO

The physiological functions of organs are intercommunicated occurring through secreted molecules. That exercise can improve the physiological function of organs or tissues is believed by secreting myokines from muscle to target remote organs. However, the underlying mechanism how exercise regulates the inter-organ communications remains incompletely understood yet. A recently identified myokine-irisin, primarily found in muscle and adipose and subsequently extending to bone, heart, liver and brain, provides a new molecular evidence for the inter-organ communications. It is secreted under the regulation of exercise and mediates the intercommunications between exercise and organs. To best our understanding of the regulatory mechanism, this review discusses the recent evidence involving the potential molecular pathways of the inter-organ communications, and the interactions between signalings and irisin in regulating the impact of exercise on organ functions are also discussed.


Assuntos
Fibronectinas , Músculo Esquelético , Fibronectinas/metabolismo , Músculo Esquelético/metabolismo , Exercício Físico/fisiologia , Osso e Ossos/metabolismo , Tecido Adiposo/metabolismo
12.
Nutrients ; 14(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36235734

RESUMO

Chronic kidney disease (CKD) commonly occurs with vitamin K (VK) deficiency and impaired bone mineralization. However, there are no data explaining the metabolism of endogenous VK and its role in bone mineralization in CKD. In this study, we measured serum levels of phylloquinone (VK1), menaquinone 4 and 7 (MK4, MK7), and VK-dependent proteins: osteocalcin, undercarboxylated osteocalcin (Glu-OC), and undercarboxylated matrix Gla protein (ucMGP). The carboxylated osteocalcin (Gla-OC), Glu-OC, and the expression of genes involved in VK cycle were determined in bone. The obtained results were juxtaposed with the bone mineral status of rats with CKD. The obtained results suggest that the reduced VK1 level observed in CKD rats may be caused by the accelerated conversion of VK1 to the form of menaquinones. The bone tissue possesses all enzymes, enabling the conversion of VK1 to menaquinones and VK recycling. However, in the course of CKD with hyperparathyroidism, the intensified osteoblastogenesis causes the generation of immature osteoblasts with impaired mineralization. The particular clinical significance seems to have a finding that serum osteocalcin and Glu-OC, commonly used biomarkers of VK deficiency, could be inappropriate in CKD conditions, whereas Gla-OC synthesized in bone appears to have an adverse impact on bone mineral status in this model.


Assuntos
Insuficiência Renal Crônica , Deficiência de Vitamina K , Animais , Biomarcadores , Osso e Ossos/metabolismo , Minerais/metabolismo , Osteocalcina , Ratos , Insuficiência Renal Crônica/complicações , Vitamina K , Vitamina K 1 , Vitamina K 2 , Deficiência de Vitamina K/etiologia
13.
Oxid Med Cell Longev ; 2022: 9110449, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275904

RESUMO

Background: Bone nonunion is a serious complication of fracture. This study explored the differentially expressed lncRNAs (DELs) and mRNAs (DEGs) and identified potential lncRNA-mRNA interactions in bone nonunion. Methods: We extracted total RNA from three bone nonunion and three bone union patient tissue samples. RNA sequencing was performed to detect DELs and DEGs between bone nonunion and union tissue samples. The lncRNAs and genes with absolute log2-fold change (log2FC) > 1 and adjusted p value < 0.05 were further chosen for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. lncRNA and targeted mRNA interaction networks were constructed. Results: We observed 179 DELs and 415 DEGs between the bone nonunion and union tissue samples. GO analysis indicated that DELs and DEGs were mainly enriched in the chondroitin sulfate proteoglycan biosynthetic process. DELs and DEGs were enriched in "ECM-receptor interaction" and "Staphylococcus aureus infection" KEGG pathways. Several potential lncRNA-mRNA interactions were also predicted. Conclusions: This study identified bone nonunion-associated lncRNAs and mRNAs using deep sequencing that may be useful as potential biomarkers for bone nonunion.


Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , Proteoglicanas de Sulfatos de Condroitina/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma/genética , Osso e Ossos/metabolismo
14.
Cells ; 11(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36291143

RESUMO

Skeletal shape and mechanical properties define, to a large extent, vertebrate morphology and physical capacities. During development, skeletal morphogenesis results from dynamic communications between chondrocytes, osteoblasts, osteoclasts, and other cellular components of the skeleton. Later in life, skeletal integrity depends on the regulatory cascades that assure the equilibrium between bone formation and resorption. Finally, during aging, skeletal catabolism prevails over anabolism resulting in progressive skeletal degradation. These cellular processes depend on the transcriptional cascades that control cell division and differentiation in each cell type. Most Distal-less (Dlx) homeobox transcription factors are directly involved in determining the proliferation and differentiation of chondrocytes and osteoblasts and, indirectly, of osteoclasts. While the involvement of Dlx genes in the regulation of skeletal formation has been well-analyzed thanks to several mutant mouse models, the role of these genes in the maintenance of bone integrity has been only partially studied. The importance of Dlx genes for adult bone tissues is evidenced by their central role in the regulatory pathways involving Osx/Sp7 and Runx2, the two major master genes of osteogenesis. Dlx genes appear to be involved in several bone pathologies including, for example, osteoporosis. Indeed, at least five large-scale GWAS studies which aimed to detect loci associated with human bone mineral density (BMD) have identified a known DLX5/6 regulatory region within chromosome 7q21.3 in proximity of SEM1/FLJ42280/DSS1 coding sequences, suggesting that DLX5/6 expression is critical in determining healthy BMD. This review aims to summarize the major findings concerning the involvement of Dlx genes in skeletal development and homeostasis and their involvement in skeletal aging and pathology.


Assuntos
Desenvolvimento Ósseo , Osso e Ossos , Proteínas de Homeodomínio , Fatores de Transcrição , Animais , Humanos , Camundongos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Desenvolvimento Ósseo/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Vertebrados/genética , Vertebrados/crescimento & desenvolvimento
15.
Exp Clin Endocrinol Diabetes ; 130(10): 671-677, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36257297

RESUMO

Advanced glycation end products (AGEs), the compounds resulting from the non-enzymatic glycosylation between reducing sugars and proteins, are derived from food or produced de novo. Over time, more and more endogenous and exogenous AGEs accumulate in various organs such as the liver, kidneys, muscle, and bone, threatening human health. Among these organs, bone is most widely reported. AGEs accumulating in bone reduce bone strength by participating in bone structure formation and breaking bone homeostasis by binding their receptors to alter the proliferation, differentiation, and apoptosis of cells involved in bone remodeling. In this review, we summarize the research about the effects of AGEs on bone health and highlight their associations with bone health in diabetes patients to provide some clues toward the discovery of new treatment and prevention strategies for bone-related diseases caused by AGEs.


Assuntos
Diabetes Mellitus , Produtos Finais de Glicação Avançada , Humanos , Produtos Finais de Glicação Avançada/metabolismo , Densidade Óssea , Diabetes Mellitus/metabolismo , Osso e Ossos/metabolismo , Açúcares , Receptor para Produtos Finais de Glicação Avançada
16.
Nutrients ; 14(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36145151

RESUMO

The adipose and bone tissues demonstrate considerable interconnected endocrine function. In the present study, we determined the concentrations of fibroblast growth factor-23 (FGF-23), osteopontin, neutrophil gelatinase-associated lipocalin (NGAL) and sclerostin in 345 children and adolescents who were overweight or obese (mean age ± SD mean: 10.36 ± 0.16 years; 172 males, 173 females; 181 prepubertal; and 164 pubertal) before and after their participation in a comprehensive life-style intervention program of diet and exercise for one year. Following the one-year life-style interventions, there was a significant decrease in BMI (p < 0.01), FGF-23 (p < 0.05), osteopontin (p < 0.01) and NGAL (p < 0.01), and an increase in sclerostin (p < 0.01) concentrations. BMI z-score (b = 0.242, p < 0.05) and fat mass (b = 0.431, p < 0.05) were the best positive predictors and waist-to-height ratio (WHtR) (b = -0.344, p < 0.05) was the best negative predictor of the change of osteopontin. NGAL concentrations correlated positively with HbA1C (b = 0.326, p < 0.05), WHtR (b = 0.439, p < 0.05) and HOMA-IR (b = 0.401, p < 0.05), while BMI (b = 0.264, p < 0.05), fat mass (b = 1.207, p < 0.05), HDL (b = 0.359, p < 0.05) and waist circumference (b = 0.263, p < 0.05) were the best positive predictors of NGAL. These results indicate that FGF-23, osteopontin, NGAL and sclerostin are associated with being overweight or obese and are altered in relation to alterations in BMI. They also indicate a crosstalk between adipose tissue and bone tissue and may play a role as potential biomarkers of glucose metabolism. Further studies are required to delineate the physiological mechanisms underlying this association in children and adolescents.


Assuntos
Sobrepeso , Obesidade Pediátrica , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Biomarcadores , Índice de Massa Corporal , Osso e Ossos/metabolismo , Criança , Dieta , Exercício Físico , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose , Hemoglobina A Glicada/metabolismo , Humanos , Lipocalina-2 , Masculino , Osteopontina/metabolismo , Sobrepeso/complicações , Sobrepeso/terapia , Obesidade Pediátrica/complicações , Obesidade Pediátrica/terapia
17.
Adv Healthc Mater ; 11(19): e2200195, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057996

RESUMO

Osteosarcoma (OS) is the most common primary bone cancer, where the overall 5-year surviving rate is below 20% in resistant forms. Accelerating cures for those poor outcome patients remains a challenge. Nevertheless, several studies of agents targeting abnormal cancerous pathways have yielded disappointing results when translated into clinic because of the lack of accurate OS preclinical modeling. So, any effort to design preclinical drug testing may consider all inter-, intra-, and extra-tumoral heterogeneities throughout models mimicking extracellular and immune microenvironment. Therefore, the bioengineering of patient-derived models reproducing the OS heterogeneity, the interaction with tumor-associated macrophages (TAMs), and the modulation of oxygen concentrations additionally to recreation of bone scaffold is proposed here. Eight 2D preclinical models mimicking several OS clinical situations and their TAMs in hypoxic conditions are developed first and, subsequently, the paired 3D models faithfully preserving histological and biological characteristics are generated. It is possible to shape reproducibly M2-like macrophages cultured with all OS patient-derived cell lines in both dimensions. The final 3D models pooling all heterogeneity features are providing accurate proliferation and migration data to understand the mechanisms involved in OS and immune cells/biomatrix interactions and sustained such that engineered 3D preclinical systems will improve personalized medicine.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/patologia , Osso e Ossos/metabolismo , Linhagem Celular Tumoral , Matriz Extracelular/metabolismo , Humanos , Osteossarcoma/metabolismo , Oxigênio , Microambiente Tumoral
18.
Radiat Res ; 198(5): 449-457, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048804

RESUMO

A baseline compartmental model (relative to modeling decorporation) of the distribution and retention of plutonium (Pu) in the rat for a systemic intake is derived. The model is derived from data obtained from a study designed to evaluate the behavior of plutonium in the first 28 days after incorporation. The model is based on a recently published model of americium (Am) in rats, which incorporated a pharmacokinetic (PK)-front-end modeling approach, which was used to specify transfer to and from the extracellular fluids (ECF) in the various tissues in terms of vascular flow and volumes of ECF. In the americium model, the approach was "cell-membrane limited," meaning that rapid diffusion of americium occurred throughout all the extracellular fluids (i.e., the blood plasma and interstitial fluids), while back-end rates representing transport into and out of the cells were determined empirically. However, this approach was inconsistent with the plutonium dataset. A good fit to the data is obtained by incorporating aspects of the Durbin et al. model structure, with plutonium in plasma separated into "free" and "bound" components. Free plutonium uses a cell-membrane-limited front end as for americium. Bound plutonium uses a capillary-wall-limited front end, where transfer rates from blood plasma into the interstitial fluids are relatively slow, and must be determined either empirically or from a priori knowledge. As in the Durbin et al. model, both free and bound plutonium are available for deposition in bone. In addition, our model has some bound plutonium associated with uptake to the gastrointestinal (GI) tract. Uncertainties in transfer rates were investigated using Markov Chain Monte Carlo (MCMC). It is anticipated that this model structure of plutonium will also be useful in interpreting comparable data from decorporation studies done in experimental animals.


Assuntos
Plutônio , Animais , Ratos , Plutônio/metabolismo , Amerício/metabolismo , Método de Monte Carlo , Transporte Biológico , Osso e Ossos/metabolismo
19.
Toxicol Pathol ; 50(7): 895-897, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36114676

RESUMO

During this presentation, a variety of class effects were reviewed by their differing effects on bone, including inhibition of endochondral ossification, inhibition of the growth hormone-insulin-like growth factor 1 axis, promotion of bone formation, inhibition of bone formation, abnormal bone formation, promotion of bone resorption, inhibition of bone resorption, and bone necrosis.


Assuntos
Reabsorção Óssea , Osso e Ossos , Humanos , Osso e Ossos/metabolismo , Osteogênese
20.
J Bone Miner Res ; 37(11): 2201-2214, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36069368

RESUMO

Excess in growth hormone (GH) levels, seen in patients with acromegaly, is associated with increases in fractures. This happens despite wider bones and independent of bone mineral density. We used the bovine GH (bGH) transgenic mice, which show constitutive excess in GH and insulin-like growth factor 1 (IGF-1) in serum and tissues, to study how lifelong increases in GH and IGF-1 affect skeletal integrity. Additionally, we crossed the acid labile subunit (ALS) null (ALSKO) to the bGH mice to reduce serum IGF-1 levels. Our findings indicate sexually dimorphic effects of GH on cortical and trabecular bone. Male bGH mice showed enlarged cortical diameters, but with marrow cavity expansion and thin cortices as well as increased vascular porosity that were associated with reductions in diaphyseal strength and stiffness. In contrast, female bGH mice presented with significantly smaller-diameter diaphysis, with greater cortical bone thickness and with a slightly reduced tissue elastic modulus (by microindentation), ultimately resulting in overall stronger, stiffer bones. We found increases in C-terminal telopeptide of type 1 collagen and procollagen type 1 N propeptide in serum, independent of circulating IGF-1 levels, indicating increased bone remodeling with excess GH. Sexual dimorphism in response to excess GH was also observed in the trabecular bone compartment, particularly at the femur distal metaphysis. Female bGH mice preserved their trabecular architecture during aging, whereas trabecular bone volume in male bGH mice significantly reduced and was associated with thinning of the trabeculae. We conclude that pathological excess in GH results in sexually dimorphic changes in bone architecture and gains in bone mass that affect whole-bone mechanical properties, as well as sex-specific differences in bone material properties. © 2022 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Acromegalia , Fator de Crescimento Insulin-Like I , Bovinos , Masculino , Animais , Feminino , Camundongos , Fator de Crescimento Insulin-Like I/metabolismo , Osso e Ossos/metabolismo , Densidade Óssea , Camundongos Transgênicos , Colágeno Tipo I
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...