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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.
J R Soc Interface ; 20(198): 20220803, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695019

RESUMO

Mineralized collagen fibrils (MCFs) comprise collagen molecules and hydroxyapatite (HAp) crystals and are considered universal building blocks of bone tissue, across different bone types and species. In this study, we developed a coarse-grained molecular dynamics (CGMD) framework to investigate the role of mineral arrangement on the load-deformation behaviour of MCFs. Despite the common belief that the collagen molecules are responsible for flexibility and HAp minerals are responsible for stiffness, our results showed that the mineral phase was responsible for limiting collagen sliding in the large deformation regime, which helped the collagen molecules themselves undergo high tensile loading, providing a substantial contribution to the ultimate tensile strength of MCFs. This study also highlights different roles for the mineralized and non-mineralized protofibrils within the MCF, with the mineralized groups being primarily responsible for load carrying due to the presence of the mineral phase, while the non-mineralized groups are responsible for crack deflection. These results provide novel insight into the load-deformation behaviour of MCFs and highlight the intricate role that both collagen and mineral components have in dictating higher scale bone biomechanics.


Assuntos
Colágeno , Simulação de Dinâmica Molecular , Colágeno/química , Osso e Ossos , Matriz Extracelular , Fenômenos Biomecânicos , Minerais/química
3.
Compr Physiol ; 13(1): 4355-4386, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36715278

RESUMO

Changes in bone architecture and metabolism with aging increase the likelihood of osteoporosis and fracture. Age-onset osteoporosis is multifactorial, with contributory extrinsic and intrinsic factors including certain medical problems, specific prescription drugs, estrogen loss, secondary hyperparathyroidism, microenvironmental and cellular alterations in bone tissue, and mechanical unloading or immobilization. At the histological level, there are changes in trabecular and cortical bone as well as marrow cellularity, lineage switching of mesenchymal stem cells to an adipogenic fate, inadequate transduction of signals during skeletal loading, and predisposition toward senescent cell accumulation with production of a senescence-associated secretory phenotype. Cumulatively, these changes result in bone remodeling abnormalities that over time cause net bone loss typically seen in older adults. Age-related osteoporosis is a geriatric syndrome due to the multiple etiologies that converge upon the skeleton to produce the ultimate phenotypic changes that manifest as bone fragility. Bone tissue is dynamic but with tendencies toward poor osteoblastic bone formation and relative osteoclastic bone resorption with aging. Interactions with other aging physiologic systems, such as muscle, may also confer detrimental effects on the aging skeleton. Conversely, individuals who maintain their BMD experience a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging. © 2023 American Physiological Society. Compr Physiol 13:4355-4386, 2023.


Assuntos
Reabsorção Óssea , Osteoporose , Humanos , Osso e Ossos , Osteoporose/etiologia , Osteoporose/patologia , Reabsorção Óssea/patologia , Osteogênese
4.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 58(1): 86-91, 2023 Jan 09.
Artigo em Chinês | MEDLINE | ID: mdl-36642458

RESUMO

Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.


Assuntos
Osso e Ossos , Nanotubos , Animais , Osteoclastos , Biologia , Comunicação Celular/fisiologia
5.
J Mech Behav Biomed Mater ; 138: 105662, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36630755

RESUMO

Metastatic bone disease occurs in 70-80% of advanced breast cancer patients and bone tissue is accepted to have attractive physical properties that facilitate cancer cell attraction, adhesion, and invasion. Bone cells also facilitate tumour invasion by biochemical signalling and through resorption of the bone matrix (osteolysis), which releases factors that further stimulate tumour cell activity. The evolving mechanical environment during tumour invasion might play an important role in these processes, as the activity of both bone and cancer cells is regulated by mechanical cues. In particular bone loss and altered mineralisation have been reported, yet how these alter the mechanical environment local to bone and tumour cells is unknown. The objective of this study is to quantify changes in the mechanical environment within bone tissue, during bone metastasis and osteolytic resorption, using finite element analysis (FEA) models reconstructed from high-resolution µCT images of metastatic mouse bone. In particular, we quantify time-dependent changes in mechanical stimuli, local to and distant from an invading tumour mass, to investigate putative mechanobiological cues for osteolysis during bone metastasis. We report here that in early metastasis (3 weeks after tumour inoculation), there was a decrease in strain distribution within the proximal femur trabecular and distal cortical bone tissue. These changes in the mechanical environment preceded extensive osteolytic destruction, but coincided with the onset of early osteolysis, cortical thickening and mineralisation of proximal and distal femur bone. We propose that early changes in the mechanical environment within bone tissue may activate resorption by osteoclast cells and thereby contribute to the extensive osteolytic bone loss at later stage (6 weeks) bone metastasis.


Assuntos
Neoplasias Ósseas , Reabsorção Óssea , Osteólise , Camundongos , Animais , Osteólise/diagnóstico por imagem , Osteólise/patologia , Análise de Elementos Finitos , Osso e Ossos/patologia , Neoplasias Ósseas/patologia , Osteoclastos , Reabsorção Óssea/diagnóstico por imagem
6.
Sci Rep ; 13(1): 252, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604534

RESUMO

High-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging in vivo imaging modality for quantification of bone microarchitecture. However, extraction of quantitative microarchitectural parameters from HR-pQCT images requires an accurate segmentation of the image. The current standard protocol using semi-automated contouring for HR-pQCT image segmentation is laborious, introduces inter-operator biases into research data, and poses a barrier to streamlined clinical implementation. In this work, we propose and validate a fully automated algorithm for segmentation of HR-pQCT radius and tibia images. A multi-slice 2D U-Net produces initial segmentation predictions, which are post-processed via a sequence of traditional morphological image filters. The U-Net was trained on a large dataset containing 1822 images from 896 unique participants. Predicted segmentations were compared to reference segmentations on a disjoint dataset containing 386 images from 190 unique participants, and 156 pairs of repeated images were used to compare the precision of the novel and current protocols. The agreement of morphological parameters obtained using the predicted segmentation relative to the reference standard was excellent (R2 between 0.938 and > 0.999). Precision was significantly improved for several outputs, most notably cortical porosity. This novel and robust algorithm for automated segmentation will increase the feasibility of using HR-pQCT in research and clinical settings.


Assuntos
Osso e Ossos , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Tíbia/diagnóstico por imagem , Rádio (Anatomia) , Extremidade Superior , Densidade Óssea
7.
Sci Data ; 10(1): 34, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653365

RESUMO

Models and simulations of human function impact medicine and medical technology. Particularly, musculoskeletal modeling provides an avenue for insight into the human body, which might not be otherwise possible. However, reaching the ultimate goal of functional multi-scale human models has been slowed by the lack of freely available datasets of anatomical models and geometries. Moreover, female-specific geometries have been neglected with a widespread emphasis on male geometry. To help realize this goal, we have developed and shared complete three-dimensional musculoskeletal geometries extracted from the National Libraries of Medicine Visible Human Female and Male cryosections. Muscle, bone, cartilage, ligament, and fat from the pelvis to the ankle were digitized and exported. These geometries provide a foundation for continued work in human musculoskeletal simulation with high-fidelity deformable tissues that enable a better understanding of normal function and the evaluation of pathologies and treatments. This work is novel as it includes both the male and female Visible Human specimens, outputs at multiple levels of post-processing for maximum data reuse, and is publicly available.


Assuntos
Extremidade Inferior , Feminino , Humanos , Masculino , Osso e Ossos , Simulação por Computador , Extremidade Inferior/anatomia & histologia , Extremidade Inferior/fisiologia
8.
Elife ; 122023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656634

RESUMO

The past decade has seen significant advances in our understanding of skeletal homeostasis and the mechanisms that mediate the loss of bone integrity in disease. Recent breakthroughs have arisen mainly from identifying disease-causing mutations and modeling human bone disease in rodents, in essence, highlighting the integrative nature of skeletal physiology. It has become increasingly clear that bone cells, osteoblasts, osteoclasts, and osteocytes, communicate and regulate the fate of each other through RANK/RANKL/OPG, liver X receptors (LXRs), EphirinB2-EphB4 signaling, sphingolipids, and other membrane-associated proteins, such as semaphorins. Mounting evidence also showed that critical developmental pathways, namely, bone morphogenetic protein (BMP), NOTCH, and WNT, interact each other and play an important role in postnatal bone remodeling. The skeleton communicates not only with closely situated organs, such as bone marrow, muscle, and fat, but also with remote vital organs, such as the kidney, liver, and brain. The metabolic effect of bone-derived osteocalcin highlights a possible role of skeleton in energy homeostasis. Furthermore, studies using genetically modified rodent models disrupting the reciprocal relationship with tropic pituitary hormone and effector hormone have unraveled an independent role of pituitary hormone in skeletal remodeling beyond the role of regulating target endocrine glands. The cytokine-mediated skeletal actions and the evidence of local production of certain pituitary hormones by bone marrow-derived cells displays a unique endocrine-immune-skeletal connection. Here, we discuss recently elucidated mechanisms controlling the remodeling of bone, communication of bone cells with cells of other lineages, crosstalk between bone and vital organs, as well as opportunities for treating diseases of the skeleton.


Assuntos
Osso e Ossos , Osteoblastos , Humanos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteócitos/metabolismo , Hormônios Hipofisários/metabolismo
9.
BMC Vet Res ; 19(1): 12, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658593

RESUMO

Macrodontia is the enlargement of tooth dimensions of different ethologies. This work aims to show a histological evaluation of macrodontic teeth in guinea pigs. The material was obtained from animals postmortem. Ninety structural changes derived from 24 guinea pigs were evaluated. All teeth used in the study showed macrodontic changes. The samples were decalcified, dehydrated and embedded in paraffin. Material was cut in the transverse and longitudinal planes in relation to the alveolar bone. Histological evaluation included apical bud cells, pulp cavity cells, periodontium, dentin, enamel, cementum and alveolar bone tissue. Individual elements were evaluated with respect to their morphology and distribution. Moreover, the arrangement of the individual hard tooth structures was assessed on the teeth. No atypia was found among the cells that make up the apical bud, pulp or periodontal cavity. Displacement of periodontal cells or odontoblasts towards the pulp cavity as well as disorganization of the cell system in the pulp cavity were observed. Changes in the dentine ligaments and the reconstruction of the alveolar bone were also observed in areas where dentine and cement systems were affected. Dental slides were observed and showed that the enamel is also involved in structural remodelling of the pulp cavity. The histological assessment revealed that structural changes in macrodontic teeth involve the rearrangement of typical tooth tissues.


Assuntos
Dente , Cobaias , Animais , Bochecha , Dente/anatomia & histologia , Osso e Ossos , Polpa Dentária
10.
Rev Med Suisse ; 19(N° 809-10): 62-65, 2023 Jan 18.
Artigo em Francês | MEDLINE | ID: mdl-36660840

RESUMO

The year 2022 has seen numerous studies: questioning the usefulness of vitamin D, the effect of osteoporosis treatments on mortality, and the benefit of parathyroidectomy on fractures in primary hyperparathyroidism. The efficacy of romosozumab is diminished by the treatments prescribed before its introduction. Finally, and fortunately, promising new molecules are available in various countries for the treatment of rare bone diseases.


L'année 2022 a vu de nombreuses études questionner l'utilité de la vitamine D et s'intéresser à l'effet des traitements de l'ostéoporose sur la mortalité ou encore au bénéfice de la parathyroïdectomie sur les fractures lors d'hyperparathyroïdie primaire. L'efficacité du romosozumab est diminuée selon les traitements prescrits avant son introduction. Finalement, et heureusement, de nouvelles molécules prometteuses sont disponibles dans différents pays pour le traitement des maladies osseuses rares.


Assuntos
Conservadores da Densidade Óssea , Doenças Ósseas , Fraturas Ósseas , Osteoporose , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Vitamina D/uso terapêutico , Osso e Ossos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico
11.
Drug Deliv ; 30(1): 2168791, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36688268

RESUMO

The clinical diagnosis and treatment of malignant bone tumors are still major clinical challenges due to their high incidence are difficulty. Targeted therapies have become a critical approach to treat bone tumors. In recent years, radiopharmaceuticals have been used widely and have shown potent and efficient results in treating bone tumors, among which 32P and the labeled radiopharmaceuticals play an essential role. In this study, the 32P-labeled hydroxyapatite (HA) was prepared through chemical synthesis (32P-Hap) and physical adsorption (32P-doped-Hap). The in vitro stability of 32P-labeled HA was analyzed to assess the superiority of the new-found chemical synthesis. The radiolabeling yield and stability of chemical synthesis (97.6 ± 0.5%) were significantly improved compared with physical adsorption (92.7 ± 0.4%). Furthermore, the CT results corroborate that 32P-Hap (100 µCi) +DOX group has the highest tumor suppression rate and can effectively reduce bone destruction. The results corroborate the effectiveness of the chemical synthesis and validate the application of 32P-Hap in bone tumors. Therefore, 32P-Hap (100 µCi) + DOX may be an effective strategy for bone metastasis treatments.


Assuntos
Neoplasias Ósseas , Nanopartículas , Humanos , Durapatita , Compostos Radiofarmacêuticos , Osso e Ossos , Neoplasias Ósseas/tratamento farmacológico
12.
Curr Biol ; 33(2): R52-R58, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36693306

RESUMO

This article begins as many others on sauropods before it: "Sauropod dinosaurs were the largest animals to ever walk the Earth, by far". The largest sauropods were easily four times heavier than the largest land mammals (and the largest other dinosaur species, for that matter). The iconic body plan of sauropods is dominated by their very long neck, in some species exceeding 14 meters in length, provided with a relatively small head (Figure 1). The neck was mostly held horizontally or at a low angle. The massive but relatively short trunk was supported by four columnar legs, much like in an elephant. The bones in the fore foot of sauropods are oriented vertically, and some late forms even lost their finger bones, walking on their metacarpals (middle bones of the hand). The hind leg, which bore most of the weight, has a half-upright foot. The femur (thigh bone) was the largest bone in the skeleton, like in most other true land vertebrates (amniotes). The long neck was counterbalanced by the long tail, the base of which also functioned as the anchoring region of the giant muscles that pulled back the hind leg during walking.


Assuntos
Dinossauros , Fósseis , Animais , Osso e Ossos , Dinossauros/anatomia & histologia , Mamíferos
13.
PLoS One ; 18(1): e0280684, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662887

RESUMO

OBJECTIVE: The aim of the present in vitro study was to evaluate the resistance on quasi-static forces and in the fatigue mechanical cycling of a new implant design compared to two other conventional implant designs. MATERIALS AND METHODS: Eighty-eight implants with their respective abutments were tested and distributed into four groups (n = 22 per group): Morse taper connection implant (MT group), conventional external hexagon implant (EH con group), new Collo implant of external hexagon with the smooth portion out of the bone insertion (EH out group), and new Collo implant of external hexagon with the implant platform inserted to the bone level (EH bl group). All the sets were subjected to quasi-static loading in a universal testing machine, and we measured the maximum resistance force supported by each sample. Another 12 samples from each group were submitted to the cyclic fatigue test at 4 intensities of forces (n = 3 per force): 80%, 60%, 40%, and 20%. The number of cycles supported by each sample at each force intensity was evaluated. RESULTS: The three groups of implants with external hexagon connection had similar maximum strength values of the sets (p > 0.05). Meanwhile, samples from the MT group showed the highest resistance values in comparison to the other three groups (p < 0.05). In the fatigue test, the Collo out group supported a smaller number of cycles that led to the fracture than the other 3 groups proposed at loads of 80%, 60%, and 40%, and only at the load value of 20% all groups had the same performance. CONCLUSIONS: Within the limitations of the present in vitro study, the results showed that the new Collo implant performs better when installed at bone level.


Assuntos
Osso e Ossos , Implantes Dentários , Análise do Estresse Dentário , Dente Suporte
14.
Cells ; 12(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36672248

RESUMO

The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model to study the regeneration of the bone-tendon-muscle interface. The 3D model was prepared from collagen and agarose, with different concentrations of hydroxyapatite to graduate the tissues from bones to muscles, resulting in a stiffness gradient. This graduated structure was fabricated using indirect 3D printing to provide biologically relevant surface topographies. MG-63, human dermal fibroblasts, and Sket.4U cells were found suitable cell models for bones, tendons, and muscles, respectively. The biphasic and triphasic hydrogels composing the 3D model were shown to be suitable for cell growth. Cells were co-cultured on the 3D model for over 21 days before assessing cell proliferation, metabolic activity, viability, cytotoxicity, tissue-specific markers, and matrix deposition to determine interface formations. The studies were conducted in a newly developed growth chamber that allowed cell communication while the cell culture media was compartmentalised. The 3D model promoted cell viability, tissue-specific marker expression, and new matrix deposition over 21 days, thereby showing promise for the development of new interfaces.


Assuntos
Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Tendões , Osso e Ossos , Cartilagem , Músculos
15.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675115

RESUMO

This study aimed to establish a surface modification technology for ZK60 magnesium alloy implants that can degrade uniformly over time and promote bone healing. It proposes a special micro-arc oxidation (MAO) treatment on ZK60 alloy that enables the composite electrolytes to create a coating with better corrosion resistance and solve the problems of uneven and excessive degradation. A magnesium alloy bone screw made in this way was able to promote the bone healing reaction after implantation in rabbits. Additionally, it was found that the MAO-treated samples could be sustained in simulated body-fluid solution, exhibiting excellent corrosion resistance and electrochemical stability. The Ca ions deposited in the MAO coating were not cytotoxic and were beneficial in enhancing bone healing after implantation.


Assuntos
Osso e Ossos , Magnésio , Animais , Coelhos , Magnésio/farmacologia , Magnésio/química , Corrosão , Próteses e Implantes , Ligas/farmacologia , Ligas/química , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
16.
Elife ; 122023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598122

RESUMO

MicroRNA-155 (miR155) is overexpressed in various inflammatory diseases and cancer, in which bone resorption and osteolysis are frequently observed. However, the role of miR155 on osteogenesis and bone mass phenotype is still unknown. Here, we report a low bone mass phenotype in the long bone of Mir155-Tg mice compared with wild-type mice. In contrast, Mir155-KO mice showed a high bone mass phenotype and protective effect against inflammation-induced bone loss. Mir155-KO mice showed robust bone regeneration in the ectopic and orthotopic model, but Mir155-Tg mice showed compromised bone regeneration compared with the wild-type mice. Similarly, the osteogenic differentiation potential of bone marrow stromal stem cells (BMSCs) from Mir155-KO mice was robust and Mir155-Tg was compromised compared with that of wild-type mice. Moreover, Mir155 knockdown in BMSCs from wild-type mice showed higher osteogenic differentiation potential, supporting the results from Mir155-KO mice. TargetScan analysis predicted sphingosine 1-phosphate receptor-1 (S1pr1) as a target gene of Mir155, which was further confirmed by luciferase assay and Mir155 knockdown. S1pr1 overexpression in BMSCs robustly promoted osteogenic differentiation without affecting cell viability and proliferation. Furthermore, osteoclastogenic differentiation of Mir155-Tg bone marrow-derived macrophages was inhibited compared with that of wild-type mice. Thus, Mir155 showed a catabolic effect on osteogenesis and bone mass phenotype via interaction with the S1pr1 gene, suggesting inhibition of Mir155 as a potential strategy for bone regeneration and bone defect healing.


Assuntos
MicroRNAs , Osteogênese , Camundongos , Animais , Osso e Ossos/metabolismo , Densidade Óssea , Diferenciação Celular , Células da Medula Óssea/metabolismo , Células Cultivadas , MicroRNAs/genética , MicroRNAs/metabolismo
17.
J Mech Behav Biomed Mater ; 138: 105633, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603527

RESUMO

3D printing technology provides a platform to fabricate a wide range of structures and complex geometry-based scaffolds through computer-aided design (CAD). This study investigates the possibility of developing Bentonite(BEN)/Hydroxyapatite(HAP) scaffold with different HAP wt% (25, 50, 75) using a 3D printing technique (Robocasting) for potential bone tissue applications. Thermal stability of the composites was characterized in TGA and rheological properties of slurries were observed to have different viscosity and shear stress, especially BEN-HAP 50 wt% achieves all criteria for high-quality printing. The fabricated scaffolds were subjected to sintering from 200 °C to 1000 °C for proper densification and attained a maximum compression strength of 52 MPa at 1000 °C for the printed structures. Changes in crystallinity and functional groups were observed as well with respective sintering temperatures. In this study, we also discussed the extrusion and rheological properties of the composite slurry. Porosity, water absorption, degradation and density were studied to understand the physical properties of the sintered scaffolds. The biological characteristics of the scaffold were studied using MG63 cell lines In vitro biocompatibility study and expressed 91% of viability for the 1000 °C sintered samples under controlled culture conditions.


Assuntos
Engenharia Tecidual , Tecidos Suporte , Tecidos Suporte/química , Engenharia Tecidual/métodos , Argila , Teste de Materiais , Durapatita/química , Impressão Tridimensional , Osso e Ossos , Porosidade
18.
J Mech Behav Biomed Mater ; 138: 105643, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603525

RESUMO

Traditional experimental tests for characterizing bone's mechanical properties usually hypothesize a uniaxial stress condition without quantitatively evaluating the influence of spatially varying principal material orientations, which cannot accurately predict the mechanical properties distribution of bones in vivo environment. In this study, a Bayesian calibrating procedure was developed using quantified multiaxial stress to investigate cancellous bone's local anisotropic elastic performance around joints as the spatial variation of main bearing orientations. First, the bone cube specimens from the distal femur of sheep are prepared using traditional anatomical axes. The multiaxial stress state of each bone specimen is calibrated using the actual principal material orientations derived from fabric tensor at different anatomical locations. Based on the calibrated multiaxial stress state, the process of identifying mechanical properties is described as an inverse problem. Then, a Bayesian calibration procedure based on a surrogate constitutive model was developed via multiaxial stress correction to identify the anisotropic material parameters. Finally, a comparison between the experiment and simulation results is discussed by applying the optimal model parameters obtained from the Bayesian probability distribution. Compared to traditional uniaxial methods, our results prove that the calibration based on the spatial variation of the main bearing orientations can significantly improve the accuracy of characterizing regional anisotropic mechanical responses. Moreover, we determine that the actual mechanical property distribution is influenced by complicated mechanical stimulation. This study provides a novel method to evaluate the spatially varying mechanical properties of bone tissues enduring complex mechanical loading accurately and effectively. It is expected to provide more realistic mechanical design targets in vivo for a personalized artificial bone prosthesis in clinical treatment.


Assuntos
Osso e Ossos , Osso Esponjoso , Animais , Ovinos , Teorema de Bayes , Calibragem , Estresse Mecânico , Anisotropia , Fenômenos Biomecânicos
19.
J Mech Behav Biomed Mater ; 138: 105636, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608532

RESUMO

Exposure to X-ray radiation for an extended amount of time can cause damage to the bone tissue and therefore affect its mechanical properties. Specifically, high-resolution X-ray Computed Tomography (XCT), in both synchrotron and lab-based systems, has been employed extensively for evaluating bone micro-to-nano architecture. However, to date, it is still unclear how long exposures to X-ray radiation affect the mechanical properties of trabecular bone, particularly in relation to lab-XCT systems. Indentation has been widely used to identify local mechanical properties such as hardness and elastic modulus of bone and other biological tissues. The purpose of this study is therefore, to use indentation and XCT-based investigative tools such as digital volume correlation (DVC) to assess the microdamage induced by long exposure of trabecular bone tissue to X-ray radiation and how this affects its local mechanical properties. Trabecular bone specimens were indented before and after X-ray exposures of 33 and 66 h, where variation of elastic modulus was evaluated at every stage. The resulting elastic modulus was decreased, and micro-cracks appeared in the specimens after the first long X-ray exposure and crack formation increased after the second exposure. High strain concentration around the damaged tissue exceeding 1% was also observed from DVC analysis. The outcomes of this study show the importance of designing appropriate XCT-based experiments in lab systems to avoid degradation of the bone tissue mechanical properties due to radiation and these results will help to inform future studies that require long X-ray exposure for in situ experiments or generation of reliable subject-specific computational models.


Assuntos
Osso e Ossos , Osso Esponjoso , Osso Esponjoso/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Módulo de Elasticidade
20.
J Mech Behav Biomed Mater ; 138: 105656, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36623402

RESUMO

In this research, a new lattice structure based on the octagonal geometry and produced by Additive Manufacturing (AM) technique was proposed. Eight octagons with the same dimensions are combined to each other forming a ring. To obtain an isotropic lattice structure, cubic symmetry was imposed; thus, the unit cell is made of three rings mutually perpendicular, one ring for each principal direction. The aim of this study is the morphological and mechanical characterization of the novel unit cell to check its suitability to the biomechanical field, along with its comparison with other lattice structures currently used as bone scaffold. Electron Beam Melting (EBM) technique was used to produce Ti6Al4V ELI alloy specimens of the novel unit cell and of the truncated octahedron (Kelvin) cell. Three different unit cell sizes were selected to investigate the effect of cell dimensions on the mechanical properties. Morphological analysis was performed through a scanning electron microscope (SEM), to compare the actual structures to the designed ones. On the whole, the new lattice structure provided adequate mechanical properties to be considered as a bone substitute; further tests will be focused on its osteointegration capability.


Assuntos
Biomimética , Osso e Ossos , Porosidade , Teste de Materiais , Próteses e Implantes , Ligas , Titânio/química
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