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1.
Am J Clin Nutr ; 112(4): 1120-1131, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32678420

RESUMO

BACKGROUND: The importance of dietary acid load (DAL) in the pathogenesis of osteoporosis is still debated. Age-related changes in bone microstructure and strength in relation to DAL remain largely unexplored. OBJECTIVES: We investigated the associations between changes in areal and volumetric bone mineral density (BMD), bone microstructure and strength, fracture risk, and DAL in a prospective cohort of 65-y-old healthy men and postmenopausal women. METHODS: Potential renal acid load (PRAL; mEq/d) was calculated as a DAL proxy to characterize participants' diet as alkaline (Alk-D; PRAL < -5), neutral (Neut-D; -5 ≤ PRAL ≤ 5), or acidic (Acid-D; PRAL >5). We measured areal BMD (aBMD) by DXA, and distal radius and tibia bone microstructure using high-resolution peripheral quantitative computed tomography, at baseline (n = 853) and after 6.1 ± 1.4 y (n = 708). Bone strength was estimated using finite element analyses at baseline and after 3.0 ± 0.5 y (n = 613). Prevalent and incident fractures were recorded. RESULTS: The majority of the participants (59%) had an Alk-D, while 23% had a Neut-D, and 18% an Acid-D. Baseline aBMD and bone microstructure and strength did differ or were slightly better in women or men with an Acid-D versus those consuming an Alk-D or Neut-D. Indeed, women with an Acid-D had higher trabecular number (P = 0.010 vs. Alk-D; P = 0.001 vs. Neut-D), while men had higher hip and radius aBMD (P = 0.008 and 0.024 vs. Neut-D, respectively) and radius strength (P = 0.026 vs. Neut-D). Over the follow-up, women in the Acid-D group experienced lower cortical and endocortical bone loss at the radius than did the Alk-D and Neut-D groups (cortical thickness, P = 0.008 and < 0.001; trabecular area, P = 0.001 and < 0.001, respectively). No association between fractures and PRAL was observed. CONCLUSIONS: These null or favourable associations between baseline values or changes in aBMD, bone microstructure and strength, and DAL in this cohort of 65-y-old healthy individuals do not support adverse DAL-mediated effects on bone. This trial was registered at http://www.isrctn.com as ISRCTN11865958.


Assuntos
Envelhecimento/metabolismo , Densidade Óssea , Osso e Ossos/ultraestrutura , Fraturas por Osteoporose/etiologia , Idoso , Estudos Transversais , Dieta , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa , Estudos Prospectivos
2.
Actual. osteol ; 16(1): 47-66, Ene - abr. 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1140035

RESUMO

La "razón de ser" de nuestros huesos y esqueletos constituye un dilema centralizado en los conceptos biológicos de "estructura" y "organización", cuya solución necesitamos comprender para interpretar, diagnosticar, tratar y monitorear correctamente las osteopatías fragilizantes. Últimamente se ha reunido conocimiento suficiente para proponer aproximaciones razonables a ese objetivo. La que exponemos aquí requiere la aplicación de no menos de 6 criterios congruentes: 1) Un criterio cosmológico, que propone un origen común para todas las cosas; 2) Un criterio biológico, que explica el origen común de todos los huesos; 3) Un enfoque epistemológico, que desafía nuestra capacidad de comprensión del concepto concreto de estructura y del concepto abstracto de organización, focalizada en la noción rectora de direccionalidad espacial; 4) Una visión ecológica, que destaca la importancia del entorno mecánico de cada organismo para la adecuación de la calidad mecánica de sus huesos a las "funciones de sostén" que les adjudicamos; 5) Una correlación entre todo ese conocimiento y el necesario para optimizar nuestra aptitud para resolver los problemas clínicos implicados y 6) Una jerarquización del papel celular en el manejo de las interacciones genético-ambientales necesario para asimilar todo el problema a una simple cuestión de organización direccional de la estructura de cada hueso. Solo aplicando estos 6 criterios estaríamos en condiciones de responder a la incógnita planteada por el título. La conclusión de esta interpretación de la conducta y función de los huesos debería afectar el fundamento de la mayoría de las indicaciones farmacológicas destinadas al tratamiento de la fragilidad ósea. (AU)


The nature of the general behavior of our bones as weight-bearing structures is a matter of two biological concepts, namely, structure and organization, which are relevant to properly interpret, diagnose, treat, and monitor all boneweakening diseases. Different approaches can be proposed to trace the corresponding relationships. The one we present here involves six congruent criteria, namely, 1) a cosmological proposal of a common origin for everything; 2) a biological acknowledgement of a common origin for all bones; 3) the epistemological questioning of our understanding of the concrete concept of structure and the abstract notion of organization, focused on the lead idea of directionality; 4) the ecological insight that emphasizes the relevance of the mechanical environment of every organism to the naturally-selected adjustment of the mechanical properties of their mobile bones to act as struts or levers; 5) The clinical aspects of all the alluded associations; 6) The central role of bone cells to control the genetics/ environment interactions of any individual as needed to optimize the directionality of the structure of each of his/her bones to keep their mechanical ability within physiological limits. From our point of view, we could only solve the riddle posed by the title by addressing all of these six criteria. The striking conclusion of our analysis suggests that the structure (not the mass) of every bone would be controlled not only to take care of its mechanical ability, but also to cope with other properties which show a higher priority concerning natural selection. The matter would be that this interpretation of bone behavior and 'function' should affect the rationales for most pharmacological indications currently made to take care of bone fragility. (AU)


Assuntos
Humanos , Osso e Ossos/fisiologia , Doenças Ósseas Metabólicas/diagnóstico , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/terapia , Osteoporose/diagnóstico , Osteoporose/terapia , Osso e Ossos/anatomia & histologia , Osso e Ossos/citologia , Osso e Ossos/ultraestrutura , Doenças Ósseas Metabólicas/terapia , Epigênese Genética
3.
PLoS One ; 15(3): e0229820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160208

RESUMO

Teriparatide is a bone-forming therapy for osteoporosis that increases bone quantity and texture, with uncertain action on bone geometry. No data are available regarding its influence on bone strain. To investigate teriparatide action on parameters of bone quantity and quality and on Bone Strain Index (BSI), also derived from DXA lumbar scan, based on the mathematical model finite element method. Forty osteoporotic patients with fractures were studied before and after two years of daily subcutaneous 20 mcg of teriparatide with dual X-ray photon absorptiometry to assess bone mineral density (BMD), hip structural analysis (HSA), trabecular bone score (TBS), BSI. Spine deformity index (SDI) was calculated from spine X-ray. Shapiro-Wilks, Wilcoxon and Student's t test were used for classical statistical analysis. Auto Contractive Map was used for Artificial Neural Network Analysis (ANNs). In the entire population, the ameliorations after therapy regarded BSI (-13.9%), TBS (5.08%), BMD (8.36%). HSA parameters of femoral shaft showed a worsening. Dividing patients into responders (BMD increase >10%) and non-responders, the first presented TBS and BSI ameliorations (11.87% and -25.46%, respectively). Non-responders presented an amelioration of BSI only, but less than in the other subgroup (-6.57%). ANNs maps reflect the mentioned bone quality improvements. Teriparatide appears to ameliorate not only BMD and TBS, but also BSI, suggesting an increase of bone strength that may explain the known reduction in fracture risk, not simply justified by BMD increase. BSI appears to be a sensitive index of TPD effect. ANNs appears to be a valid tool to investigate complex clinical systems.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Teriparatida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/ultraestrutura , Hormônios e Agentes Reguladores de Cálcio/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação
4.
J Bone Miner Metab ; 38(4): 456-468, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32008099

RESUMO

INTRODUCTION: The goal is to propose a material scientific hypothesis for the atomic arrangement of calcium phosphates during the mineralization of bones. MATERIALS AND METHODS: It was reached by the analysis of bones of healthy and osteoporotic rats using analytical transmission electron microscopic methods. RESULTS: Electron diffraction patterns show hydroxyapatite (HAP) as dominant phase within the mineralized areas. In the electron energy loss spectrum, a double peak of the phosphorous L-edge seems to be a characteristic feature of the phosphorous binding in biological HAP. The hypothesis bases on periodic features on the collagen surface which agree with distances between oxygen atoms in the (200) plane of octacalcium phosphate (OCP). Bridge pillars for the HAP network consist of OCP coupled with a half unit cell on collagen by oxygen-hydrogen bridges. Possibly, the metastable OCP bridges are only a transient step, while the mineralization is starting. OCP and HAP couple by similar distances of calcium atoms in an interface close to the (100) planes of the OCP and the HAP network. To reach the perfect overlap of the equidistant Ca atoms, the HAP network has to be rotated by 22.5° around the a-axis, 11.5° around the c-axis of HAP, and 10.1° around an axis perpendicular to a and c. CONCLUSIONS: A supercell based on this idea is able to explain the dominance of HAP in the electron diffraction patterns, the arrangement of the (002) lattice planes perpendicular to the collagen fiber axis, and sections of high-resolution TEM images.


Assuntos
Biomineralização/fisiologia , Osso e Ossos/fisiologia , Animais , Osso e Ossos/ultraestrutura , Fosfatos de Cálcio/química , Durapatita/química , Feminino , Minerais/química , Ratos Sprague-Dawley , Difração de Raios X
5.
Micron ; 132: 102841, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32062296

RESUMO

The histological study of hard pieces such as tendons and calcified lesions and tissues is a field that has been gaining increased attention owing to the rapid development of implantable prostheses, among other factors. In these studies, serial sectioning is utilized to detect areas of interest throughout the entire piece, as it enables the application of the appropriate light and electron microscopy techniques in these areas. We propose the "three-sectioning method" that subjects the pieces to three consecutive cycles of embedding and sectioning to localize and study the areas of interest, as an efficient technique for these histological studies. The pieces were first embedded in epoxy resin and then cut into thick sections (approximately 300 µm) for the first cycle. Next, areas of interest selected on these thick sections were re-embedded in epoxy resin to be sectioned again (second sectioning) to obtain a series of semithin sections (1-3 µm). These semithin sections are usually studied using the most relevant techniques for light microscopy. Smaller areas of interest are selected to be cut into ultrathin sections (60-90 nm) for transmission electron microscopy. If necessary, the selected areas of the semithin sections can be embedded again, and then cut into new ultrathin sections. The different kinds of sections we have described here may also be studied using scanning electron microscopy. This systematic method facilitates correlative microscopy from lower to higher magnifications along with the usage of a broad variety of histological techniques including electron microscopy.


Assuntos
Técnicas Histológicas/métodos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microtomia/métodos , Manejo de Espécimes/métodos , Animais , Osso e Ossos/ultraestrutura , Resinas Epóxi , Feminino , Masculino , Ratos Wistar , Tendões/ultraestrutura
6.
Medicine (Baltimore) ; 99(8): e19120, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080087

RESUMO

Osteoporosis (OP) is a disease characterized by bone mass loss, bone microstructure damage, increased bone fragility, and easy fracture. The molecular mechanism underlying OP remains unclear.In this study, we identified 217 genes associated with OP, and formed a gene set [OP-related genes gene set (OPgset)].The highly enriched GOs and pathways showed OPgset genes were significantly involved in multiple biological processes (skeletal system development, ossification, and osteoblast differentiation), and several OP-related pathways (Wnt signaling pathway, osteoclast differentiation, steroid hormone biosynthesis, and adipocytokine signaling pathway). Besides, pathway crosstalk analysis indicated three major modules, with first module consisted of pathways mainly involved in bone development-related signaling pathways, second module in Wnt-related signaling pathway and third module in metabolic pathways. Further, we calculated degree centrality of a node and selected ten key genes/proteins, including TGFB1, IL6, WNT3A, TNF, PTH, TP53, WNT1, IGF1, IL10, and SERPINE1. We analyze the K-core and construct three k-core sub-networks of OPgset genes.In summary, we for the first time explored the molecular mechanism underlying OP via network- and pathway-based methods, results from our study will improve our understanding of the pathogenesis of OP. In addition, these methods performed in this study can be used to explore pathogenesis and genes related to a specific disease.


Assuntos
Osso e Ossos/patologia , Fraturas Ósseas/etiologia , Osteoporose/genética , Adipocinas/genética , Densidade Óssea/genética , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , Diferenciação Celular/genética , Biologia Computacional/métodos , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Osteogênese/genética , Osteoporose/complicações , Osteoporose/epidemiologia , Prevalência , Via de Sinalização Wnt/genética
7.
Eur J Endocrinol ; 182(3): 303-311, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31940278

RESUMO

Objective: Roux-en-Y-gastric bypass (RYGB) surgery is an effective treatment for morbid obesity. A possible overlooked side effect is negative bone metabolic consequences. Design: A seven-year prospective study following ten women and seven men after RYGB (baseline mean age 43 ± 8 years, BMI 42 ± 6 kg/m2). Methods: Lumbar spine and total hip bone mineral density (BMD) using dual energy x-ray absorptiometry, distal radius and tibia bone geometry, volumetric BMD, microarchitecture and finite element estimated bone strength using high-resolution peripheral quantitative CT and biochemical markers of bone remodelling were assessed at baseline, 2 and 7 years. Results: Compared to baseline, body weight was 24 ± 10% lower after 2 years and 21 ± 11% after 7 years. During the 7 years of follow-up, radius and tibia vBMD had declined 13 ± 8% and 8 ± 7% from baseline to 2 years and further 10 ± 7% and 7 ± 8% from 2 to 7 years (all P < 0.001). At both radius and tibia, cortical thickness declined and cortical porosity increased. From baseline to 7 years, there were clear indications of deteriorations of the trabecular network with fewer, more widely spaced and more in-homogeneously distributed trabeculae in both radius and tibia. Overall, declines in estimated bone strength of 16 ± 9% in radius and 16 ± 7% in tibia were observed (both P < 0.001). Conclusion: Seven years after RYGB, evidence of continuous declines in BMD and ongoing deterioration of bone microarchitecture and reduced estimated bone strength compared to baseline and 2 years post-surgery results were found. These findings emphasize the need for regular assessment of bone health in patients with prior RYGB.


Assuntos
Anastomose em-Y de Roux/efeitos adversos , Densidade Óssea , Osso e Ossos/patologia , Complicações Pós-Operatórias/patologia , Absorciometria de Fóton , Adulto , Remodelação Óssea , Osso e Ossos/ultraestrutura , Estudos de Coortes , Feminino , Seguimentos , Quadril/patologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Coluna Vertebral/patologia
8.
Sci Adv ; 6(1): eaax6250, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911944

RESUMO

Despite its iconic status as the king of dinosaurs, Tyrannosaurus rex biology is incompletely understood. Here, we examine femur and tibia bone microstructure from two half-grown T. rex specimens, permitting the assessments of age, growth rate, and maturity necessary for investigating the early life history of this giant theropod. Osteohistology reveals these were immature individuals 13 to 15 years of age, exhibiting growth rates similar to extant birds and mammals, and that annual growth was dependent on resource abundance. Together, our results support the synonomization of "Nanotyrannus" into Tyrannosaurus and fail to support the hypothesized presence of a sympatric tyrannosaurid species of markedly smaller adult body size. Our independent data contribute to mounting evidence for a rapid shift in body size associated with ontogenetic niche partitioning late in T. rex ontogeny and suggest that this species singularly exploited mid- to large-sized theropod niches at the end of the Cretaceous.


Assuntos
Dinossauros/anatomia & histologia , Fêmur/ultraestrutura , Fósseis/ultraestrutura , Tíbia/ultraestrutura , Animais , Tamanho Corporal , Osso e Ossos/ultraestrutura , Dente/ultraestrutura
9.
Med Hypotheses ; 134: 109427, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622920

RESUMO

There have been increasing numbers of reports that anti-osteoporosis drugs cause osteonecrosis. A typical example is medication-related osteonecrosis of the jaws (MRONJ) which can cause massive necrosis and defects of the jaws. Thus, the dosage and effects of anti-osteoporosis drugs should be re-examined. Our hypothesis is that primary moderate osteoporosis itself is beneficial for bones and should not be excessively treated other than vitamin D, calcium supplementation and functional exercises. The self-repair and anti-infection abilities of bone depend on its organic tissues including stem cells, blood vessels, osteoclastic and osteogenic factors in bone, which jointly fight against invading pathogens and repair bone damage. Recent evidence supports age-related changes in mesenchymal stem cell including loss of self-renewal and increases in senescent cell numbers. Thus, the number of MSCs and vessels need to be increased to achieve functions similar to those in young people. This requires dissolving a portion of inorganic materials and providing extra space to hold more cells and blood vessels. In contrast, anti-osteoporosis drugs prevent bone destruction, and increase mineralization that occupies the space of organic materials, reduces bone immunity and self-repair. Moreover, long term use of anti-osteoporosis drugs also have negative effects on long bones and cartilages. Therefore, moderate age-related osteoporosis is natural in humans to protect bones. Excessive treatment of osteoporosis weakens immunity and self-repair.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Osso e Ossos/metabolismo , Modelos Biológicos , Osteoporose/fisiopatologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/irrigação sanguínea , Osso e Ossos/citologia , Osso e Ossos/ultraestrutura , Cálcio/uso terapêutico , Autorrenovação Celular , Senescência Celular , Terapia Combinada , Implantes Dentários , Terapia por Exercício , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Osteoporose/tratamento farmacológico , Osteoporose/terapia , Vitamina D/uso terapêutico
10.
Lasers Med Sci ; 35(7): 1477-1485, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31828574

RESUMO

The extensive research on the laser machining of the bone has been, so far, restricted to drilling and cutting that is one- and two-dimensional machining, respectively. In addition, the surface morphology of the laser machined region has rarely been explored in detail. In view of this, the current work employed three-dimensional laser machining of human bone and reports the distinct surface morphology produced within a laser machined region of human bone. Three-dimensional laser machining was carried out using multiple partially overlapped pulses and laser tracks with a separation of 0.3 mm between the centers of consecutive laser tracks to remove a bulk volume of the bone. In this study, a diode-pumped pulse Er:YAG laser (λ = 2940 nm) was employed with continuously sprayed chilled water at the irradiation site. The resulting surface morphology evolved within the laser-machined region of the bone was evaluated using scanning electron microscopy, energy dispersive spectroscopy, and X-ray micro-computed tomography. The distinct surface morphology involved cellular/channeled scaffold structure characterized by interconnected pores surrounded by solid ridges, produced within a laser machined region of human structural bone. Underlying physical phenomena responsible for evolution of such morphology have been proposed and explained with the help of a thermokinetic model.


Assuntos
Osso e Ossos/efeitos da radiação , Lasers de Estado Sólido , Osso e Ossos/ultraestrutura , Humanos , Espectrometria por Raios X , Temperatura , Fatores de Tempo , Microtomografia por Raio-X
11.
J Orthop Res ; 38(5): 972-983, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31793028

RESUMO

Advanced glycation end-products (AGEs) have been suggested to contribute to bone fragility in type 2 diabetes (T2D). AGEs can be induced through in vitro sugar incubations but there is limited data on the effect of total fluorescent AGEs on mechanical properties of human cortical bone, which may have altered characteristics in T2D. Thus, to examine the effect of AGEs on bone directly in T2D patients with uncontrolled sugar levels, it is essential to first understand the fundamental mechanisms by studying the effects of controlled in vitro-induced AGEs on cortical bone mechanical behavior. Here, human cortical bone specimens from female cadaveric tibias (ages 57-87) were incubated in an in vitro 0.6 M ribose or vehicle solution (n = 20/group) for 10 days at 37°C, their mechanical properties were assessed by microindentation and fracture toughness tests, and induced AGE levels were quantified through a fluorometric assay. Results indicated that ribose-incubated bone had significantly more AGEs (+81%, p ≤ 0.005), lower elastic modulus assessed by traditional microindentation, and lower fracture toughness compared with vehicle controls. Furthermore, based on pooled data, increased AGEs were significantly correlated with deteriorated mechanical properties. The findings presented here show that the accumulation of AGEs allows for lower stiffness and increased ability to initiate a crack in human cortical bone. Statement of clinical significance: High sugar levels as in T2D results in deteriorated bone quality via AGE accumulation with a consequent weakening in bone's mechanical integrity. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:972-983, 2020.


Assuntos
Osso e Ossos/efeitos dos fármacos , Módulo de Elasticidade/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Ribose/toxicidade , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , Feminino , Humanos , Pessoa de Meia-Idade
12.
J Synchrotron Radiat ; 27(Pt 1): 199-206, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31868752

RESUMO

This study explores the application of synchrotron radiation and conventional microcomputed tomography (SR-µCT and C-µCT, respectively) in evaluating bone-biopsy specimens. Bone-biopsy specimens were obtained using a trephine bur during bone-graft removal for implant placement six months after performing a maxillary sinus bone-graft procedure. Image data of specimens were obtained using SR-µCT and C-µCT. SR-µCT was performed using the 6C biomedical imaging beamline at the Pohang Accelerator Laboratory with a monochromatic X-ray beam of 23 keV, and C-µCT was performed using a table-top CT scanner (Skyscan 1272). Reconstruction images obtained using the two methods were qualitatively compared with 2D images evaluated under 3D visualization. The SR-µCT images, especially of the new-bone-graft-woven-bone formation, were less noisy and sharper than the C-µCT images. To evaluate the new-bone-graft-woven-bone formation, only the SR-µCT images showed areas of new bone (NB) formation with bone substitute (BS; Bio-Oss) and woven bone (WB) contact, and correctly visualized true 3D structures of bone formation. Hence, µCT techniques are non-destructive and can provide detailed images of bone biopsy. In particular, SR-µCT can be used to obtain improved image quality with contrast of NB, BS and WB, demonstrating a level of detail comparable with bone formation. SR-µCT could be an unbiased 3D alternative for imaging WB formation and for high-throughput analysis.


Assuntos
Regeneração Óssea , Osso e Ossos/ultraestrutura , Síncrotrons , Microtomografia por Raio-X/métodos , Absorção de Radiação , Biópsia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Maxila/patologia , Maxila/cirurgia , Refratometria
13.
Sci Rep ; 9(1): 16994, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740777

RESUMO

Type 1 diabetes mellitus (DM1) is linked to a decrease in bone strength. Bone strength entails both bone mineral density and bone quality. Limited data are available regarding diabetes-induced microdamage, which can severely influence bone quality. This study has investigated bone microdamage as a measure of bone quality in an animal model of DM1. Microdamage in the neck of the femur was labelled in vivo using multiple fluorochromes at 4, 12 and 24 weeks after the onset of DM1. Microcracks were quantified and their morphology analyzed using microscopy techniques. The mean length of microcracks at 24 weeks, and crack numerical and surface densities were significantly higher (p < 0.05) 4 weeks after the onset of DM1 when compared with control. Diffuse damage density was highest at 12 weeks after the onset of DM1. The arrangement of the collagen fibrils became progressively more irregular from 4 to 24 weeks of DM. This is the first study to analyze microdamage in vivo at different time points of DM1. DM1is associated with microcracks from the early stage, however bone microstructure shows toughening mechanisms that arrest their growth but disease progression further deteriorates bone quality resulting in longer microcracks which may increase fracture risk.


Assuntos
Densidade Óssea , Osso e Ossos/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Estresse Mecânico , Animais , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , Força Compressiva , Modelos Animais de Doenças , Corantes Fluorescentes/metabolismo , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/metabolismo , Fraturas Ósseas/fisiopatologia , Masculino , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Ratos Wistar , Fatores de Tempo
14.
Int J Mol Sci ; 20(20)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614903

RESUMO

The main goal of bone tissue engineering (BTE) is to refine and repair major bone defects based on bioactive biomaterials with distinct properties that can induce and support bone tissue formation. Graphene and its derivatives, such as graphene oxide (GO), display optimal properties for BTE, being able to support cell growth and proliferation, cell attachment, and cytoskeleton development as well as the activation of osteogenesis and bone development pathways. Conversely, the presence of GO within a polymer matrix produces favorable changes to scaffold morphologies that facilitate cell attachment and migration i.e., more ordered morphologies, greater surface area, and higher total porosity. Therefore, there is a need to explore the potential of GO for tissue engineering applications and regenerative medicine. Here, we aim to promote one novel scaffold based on a natural compound of chitosan, improved with 3 wt.% GO, for BTE approaches, considering its good biocompatibility, remarkable 3D characteristics, and ability to support stem cell differentiation processes towards the bone lineage.


Assuntos
Osso e Ossos/citologia , Quitosana/química , Grafite/química , Osteogênese , Engenharia Tecidual/métodos , Tecidos Suporte , Células-Tronco Adultas/citologia , Materiais Biocompatíveis/química , Regeneração Óssea , Osso e Ossos/ultraestrutura , Diferenciação Celular , Proliferação de Células , Humanos , Teste de Materiais , Conformação Molecular , Osteócitos/citologia , Osteócitos/ultraestrutura , Porosidade
15.
FASEB J ; 33(12): 13882-13892, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626573

RESUMO

Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity occurring during peripubertal growth period that affects 1-4% of adolescents globally without clear etiopathogenetic mechanism. Low bone mineral density is an independent and significant prognostic factor for curve progression. Currently, the cause underlying low bone mass in AIS remains elusive. Osteocytes play an important role in bone metabolism and mineral homeostasis, but its role in AIS has not been studied. In the present study, iliac bone tissues were harvested from 21 patients with AIS (mean age of 14.3 ± 2.20 yr old) with a mean Cobb angle of 55.6 ± 10.61° and 13 non-AIS controls (mean age of 16.5 ± 4.79 yr old) intraoperatively. Acid-etched scanning electron microscopy (SEM) images of AIS demonstrated abnormal osteocytes that were more rounded and cobblestone-like in shape and were aligned in irregular clusters with shorter and disorganized canaliculi. Further quantitative analysis with FITC-Imaris technique showed a significant reduction in the canalicular number and length as well as an increase in lacunar volume and area in AIS. SEM with energy-dispersive X-ray spectroscopy analysis demonstrated a lower calcium-to-phosphorus ratio at the perilacunar/canalicular region. Moreover, microindentaion results revealed lower values of Vickers hardness and elastic modulus in AIS when compared with controls. In addition, in the parallel study of 99 AIS (27 with severe Cobb angle of 65.8 ± 14.1° and 72 with mild Cobb angle of 26.6 ± 9.1°) with different curve severity, the serum osteocalcin level was found to be significantly and negatively associated with the Cobb angle. In summary, the findings in this series of studies demonstrated the potential link of abnormal osteocyte lacuno-canalicular network structure and function to the observed abnormal bone mineralization in AIS, which may shed light on etiopathogenesis of AIS.-Chen, H., Zhang, J., Wang, Y., Cheuk, K.-Y., Hung, A. L. H., Lam, T.-P., Qiu, Y., Feng, J. Q., Lee, W. Y. W., Cheng, J. C. Y. Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.


Assuntos
Osso e Ossos/ultraestrutura , Osteocalcina/sangue , Osteócitos/citologia , Escoliose/sangue , Absorciometria de Fóton , Adolescente , Doenças Ósseas Metabólicas/sangue , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Adulto Jovem
16.
Microsc Microanal ; 25(6): 1323-1330, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31599216

RESUMO

Mineral particles in bone are interlaced with collagen fibrils, hindering the investigation of bioapatite crystallites (BAp). This study utilized a special whale rostrum (the most highly mineralized bone ever recorded) to measure the crystallites of bone BAp via long-term dissolution in water. The BAp in the rostrum has a low solubility (6.7 ppm Ca and 3.8 ppm P after 150 days dissolution) as well as in normal bones, which leads to its Ksp value of ~10-53. Atomic force microscopy results show tightly compacted mineral crystallites and confirm the low amount of collagen in the rostrum. Additionally, the mineral crystallites demonstrate irregular plate-like shapes with variable sizes. The small crystallites (~11 × 24 nm) are easily detached from BAp prisms, compared with the large crystallites (~50 nm). Moreover, various orientations of crystallites are observed on the edge of the prisms, which suggest a random direction of mineral growth. Furthermore, these plate-like crystallites prefer to be stacked layer by layer under weak regulation from collagen. The morphology of rostrum after dissolution provides new insights into the actual morphology of BAp crystallites.


Assuntos
Apatitas/metabolismo , Osso e Ossos/química , Osso e Ossos/ultraestrutura , Colágeno/ultraestrutura , Cristalização , Baleias , Animais , Colágeno/análise , Microscopia de Força Atômica
17.
Adv Healthc Mater ; 8(21): e1901030, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31583846

RESUMO

Magnesium (Mg2+ ), as a main component of bone, is widely applied to promote bone growth and regeneration. However, Mg2+ can chemically inhibit the crystallization of amorphous calcium phosphate into hydroxyapatite (HA). The underlying mechanisms by which Mg2+ improves bone biomineralization remain elusive. Here, it is demonstrated that Mg2+ plays dual roles in bone biomineralization from a developmental perspective. During embryonic development, the Mg2+ concentration is enriched in the early stage from embryonic day 13.5 (E13.5) to E15.5, but gradually decreases to a stable state in the late phase, after E15.5. Appropriate concentrations of Mg2+ can promote the mineralization of bone marrow mesenchymal stem cells, while excessive Mg2+ impairs their osteogenesis. The earlier the Mg2+ is added, the stronger the observed inhibition of mineralization. In particular, less Mg2+ is present in fully mineralized collagen than in poorly mineralized collagen. Furthermore, a high concentration of Mg2+ changes the crystalline morphology of HA and inhibits collagen calcification. Functionally, a high-Mg2+ diet inhibits bone biomineralization in mouse offspring. Taken together, the results suggest that appropriate regulation of Mg2+ concentration over time is vital for normal biomineralization. This study is significant for the future design of bone substitutes and implants associated with Mg2+ content.


Assuntos
Regeneração Óssea/fisiologia , Osso e Ossos/metabolismo , Magnésio/metabolismo , Animais , Biomineralização , Osso e Ossos/ultraestrutura , Calcificação Fisiológica/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia Eletrônica de Varredura , Osteogênese/fisiologia , Estresse Mecânico
18.
Mater Sci Eng C Mater Biol Appl ; 105: 110020, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546350

RESUMO

In situ High-Temperature X-ray diffraction (HT-XRD) from 400 to 900 °C was carried out to obtain patterns of bio hydroxyapatite every 20 °C during calcination processes at heating rates of 3, 6, and 9 °C/min to determine changes in its structural parameters as well as in its thermal expansion coefficient (TEC) for a and c lattice parameters. Additionally, High-Resolution Transmission Electron microscopy (HR-TEM) demonstrates that this HAp has an ordered nano like plate crystalline structure. The raw sample exhibits broad X-ray peaks originated by its nano size, and after calcination at about 700 °C, these become narrowed due to crystal growth. The calculation of the TEC as a function of the temperature for this hydroxyapatite shows a nonlinear increment for the a and c lattice parameters. Lattice thermal expansion occurs as water and organic matter are lost as the coalescence of HAp crystals take place; furthermore, as the heating rate increases, so does the lattice volume. Thermal analyses confirm that crystal growth is a process that starts after the bone sample has lost all its organic material and then bio-hydroxyapatite size changes from nano to micro-scale. A simulation using the PDF-4 software confirmed the nanometric size of the hydroxyapatite.


Assuntos
Durapatita/química , Teste de Materiais/métodos , Difração de Raios X , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/ultraestrutura , Varredura Diferencial de Calorimetria , Bovinos , Durapatita/farmacologia , Temperatura Alta , Minerais/análise
19.
Mater Sci Eng C Mater Biol Appl ; 105: 110014, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546414

RESUMO

Cuttlefish bone (CB) has been explored as biomaterial in the bone tissue-engineering field due to its unique porous structure and capacity of the aragonite mineral to be hydrothermally converted into calcium phosphates (CaPs). In the present study, undoped and ion (Sr2+, Mg2+ and/or Zn2+) doped biphasic calcium phosphate (BCP) scaffolds were prepared by hydrothermal transformation (HT, 200 °C, 24 h) of CB. The obtained scaffolds were sintered and then coated with two commercial polymers, poly(ε-caprolactone) (PCL) or poly(DL-lactide) (PDLA), and with two synthesized ones, a poly(ester amide) (PEA) or a poly(ester urea) (PEU) in order to improve their compressive strength. The scaffolds were characterized by X-ray diffraction (XRD) coupled with structural Rietveld refinement, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The results demonstrate that CB could be entirely transformed into BCPs in the presence or absence of doping elements. The initial CB structure was preserved and the polymeric coatings did not jeopardize the interconnected porous structure. Furthermore, the polymeric coatings enhanced the compressive strength of the scaffolds. The in vitro bio-mineralization upon immersing the scaffolds into simulated body fluid (SBF) demonstrated the formation of bone-like apatite surface layers in both uncoated and coated scaffolds. Overall, the produced scaffolds exhibit promising properties for bone tissue engineering applications.


Assuntos
Osso e Ossos/química , Fosfatos de Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Decapodiformes/anatomia & histologia , Polímeros/farmacologia , Tecidos Suporte/química , Animais , Osso e Ossos/ultraestrutura , Calcificação Fisiológica , Força Compressiva , Módulo de Elasticidade , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Temperatura , Difração de Raios X
20.
Biomaterials ; 220: 119402, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31400612

RESUMO

Representative in vitro models that mimic the native bone tumor microenvironment are warranted to support the development of more successful treatments for bone metastases. Here, we have developed a primary cell 3D model consisting of a human osteoblast-derived tissue-engineered construct (hOTEC) indirectly co-cultured with patient-derived prostate cancer xenografts (PDXs), in order to study molecular interactions in a patient-derived microenvironment context. The engineered biomimetic microenvironment had high mineralization and embedded osteocytes, and supported a high degree of cancer cell osteomimicry at the gene, protein and mineralization levels when co-cultured with prostate cancer PDXs from a lymph node metastasis (LuCaP35) and bone metastasis (BM18) from patients with primary prostate cancer. This fully patient-derived model is a promising tool for the assessment of new molecular mechanisms and as a personalized pre-clinical platform for therapy testing for patients with prostate cancer bone metastases.


Assuntos
Biomimética , Neoplasias Ósseas/secundário , Osteoblastos/patologia , Neoplasias da Próstata/patologia , Engenharia Tecidual , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Idoso , Animais , Matriz Óssea/metabolismo , Neoplasias Ósseas/genética , Osso e Ossos/patologia , Osso e Ossos/ultraestrutura , Calcificação Fisiológica , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos NOD , Osteócitos/metabolismo , Osteócitos/ultraestrutura , Tecidos Suporte/química
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