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1.
Nat Metab ; 3(1): 11-20, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398192

RESUMO

The skeleton is diverse in its functions, which include mechanical support, movement, blood cell production, mineral storage and endocrine regulation. This multifaceted role is achieved through an interplay of osteoblasts, chondrocytes, bone marrow adipocytes and stromal cells, all generated from skeletal stem cells. Emerging evidence shows the importance of cellular metabolism in the molecular control of the skeletal system. The different skeletal cell types not only have distinct metabolic demands relating to their particular functions but also are affected by microenvironmental constraints. Specific metabolites control skeletal stem cell maintenance, direct lineage allocation and mediate cellular communication. Here, we discuss recent findings on the roles of cellular metabolism in determining skeletal stem cell fate, coordinating osteoblast and chondrocyte function, and organizing stromal support of haematopoiesis. We also consider metabolic dysregulation in skeletal ageing and degenerative diseases, and provide an outlook on how the field may evolve in the coming years.


Assuntos
Doenças Ósseas/fisiopatologia , Osso e Ossos/citologia , Animais , Células da Medula Óssea , Osso e Ossos/fisiologia , Osso e Ossos/fisiopatologia , Comunicação Celular , Linhagem da Célula , Senescência Celular , Humanos , Osteoblastos/metabolismo , Células-Tronco/metabolismo
2.
Int J Mol Sci ; 22(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498907

RESUMO

Tissue nonspecific alkaline phosphatase (TNAP/Alpl) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We investigated the impact of TNAP deficiency on bone formation, mineralization, and differentiation of bone marrow stromal cells. We also pursued studies of proliferation, mitochondrial function and ATP levels in TNAP deficient bone and muscle progenitor cells. We find that TNAP deficiency decreases trabecular bone volume fraction and trabeculation in addition to decreased mineralization. We also find that Alpl-/- mice (global TNAP knockout mice) exhibit muscle and motor coordination deficiencies similar to those found in individuals with hypophosphatasia (TNAP deficiency). Subsequent studies demonstrate diminished proliferation, with mitochondrial hyperfunction and increased ATP levels in TNAP deficient bone and muscle progenitor cells, plus intracellular expression of TNAP in TNAP+ cranial osteoprogenitors, bone marrow stromal cells, and skeletal muscle progenitor cells. Together, our results indicate that TNAP functions inside bone and muscle progenitor cells to influence mitochondrial respiration and ATP production. Future studies are required to establish mechanisms by which TNAP influences mitochondrial function and determine if modulation of TNAP can alter mitochondrial respiration in vivo.


Assuntos
Trifosfato de Adenosina/biossíntese , Fosfatase Alcalina/metabolismo , Osso e Ossos/metabolismo , Respiração Celular , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/fisiologia , Animais , Osso e Ossos/fisiologia , Calcificação Fisiológica , Diferenciação Celular , Masculino , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Knockout , Músculo Esquelético/fisiologia , Osteogênese , Crânio/metabolismo , Crânio/fisiologia
3.
Am J Physiol Endocrinol Metab ; 320(3): E415-E424, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33308013

RESUMO

Sex steroids are critical for skeletal development and maturation during puberty as well as for skeletal maintenance during adult life. However, the exact time during puberty when sex steroids have the highest impact as well as the ability of bone to recover from transient sex steroid deficiency is unclear. Surgical castration is a common technique to study sex steroid effects in rodents, but it is irreversible, invasive, and associated with metabolic and behavioral alterations. Here, we used a low dose (LD) or a high dose (HD) of gonadotropin-releasing hormone antagonist to either temporarily or persistently suppress sex steroid action in male mice, respectively. The LD group, a model for delayed puberty, did not show changes in linear growth or body composition, but displayed reduced trabecular bone volume during puberty, which fully caught up at adult age. In contrast, the HD group, representing complete pubertal suppression, showed a phenotype reminiscent of that observed in surgically castrated rodents. Indeed, HD animals exhibited severely impaired cortical and trabecular bone acquisition, decreased body weight and lean mass, and increased fat mass. In conclusion, we developed a rodent model of chemical castration that can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency.NEW & NOTEWORTHY We developed a rodent model of chemical castration, which can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency.


Assuntos
Desenvolvimento Ósseo , Osso e Ossos/fisiologia , Hormônios Esteroides Gonadais/deficiência , Hipogonadismo/patologia , Animais , Composição Corporal/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Hormônios Esteroides Gonadais/farmacologia , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/farmacologia , Hipogonadismo/complicações , Hipogonadismo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Orquiectomia , Maturidade Sexual/fisiologia , Fatores de Tempo
4.
Methods Mol Biol ; 2230: 199-215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33197016

RESUMO

One of the primary functions of bone is to support the skeleton by withstanding load. In the diseased state, bone's ability to perform this function is altered. Quantification of the features of bone that support its functional behavior, and how they may change with disease, is accomplished through mechanical testing. As such, mechanical testing is a useful tool for scientists studying orthopedic-related diseases. Furthermore, a common animal model used to investigate disease and its treatment is the mouse. Therefore, in this chapter we (1) describe central concepts of mechanical testing, (2) describe factors that influence the mechanical behavior of bone, and (3) describe the application of a widely used mechanical testing technique, four-point bending, to the mouse bone for characterization of its structural properties.


Assuntos
Osso e Ossos/fisiologia , Crânio/fisiologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Humanos , Camundongos , Suporte de Carga/fisiologia
5.
Methods Mol Biol ; 2230: 217-230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33197017

RESUMO

The bone is typically studied using traditional histology techniques, that is, serial sectioning and staining. While effective, these techniques are laborious and destructive, as the native 3D environment of the bone is not maintained. Presented here is a bone-clearing methodology, termed Bone CLARITY, which combines published techniques for clearing soft tissues, including delipidation for the removal of light-scattering membranes, hydrogel-embedding for the stabilization of fragile epitopes, heme elution for the reduction of blood-based autofluorescence; as well as specialized steps, including decalcification and progressive refractive index matching, for addressing the unique challenges posed by osseous tissue. This method renders the bone transparent and enables the detailed visualization of an intact tissue specimen at multiple spatial scales.


Assuntos
Osso e Ossos/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imagem Óptica/métodos , Coloração e Rotulagem/métodos , Animais , Osso e Ossos/fisiologia , Heme/química , Humanos , Hidrogéis/farmacologia , Camundongos , Fenótipo , Crânio/diagnóstico por imagem , Crânio/fisiologia
6.
Methods Mol Biol ; 2147: 3-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840806

RESUMO

The design of optimized scaffolds for tissue engineering and regenerative medicine is a key topic of current research, as the complex macro- and micro-architectures required for scaffold applications depend not only on the mechanical properties but also on the physical and molecular queues of the surrounding tissue within the defect site. Thus, the prediction of optimal features for tissue engineering scaffolds is very important, for both its physical and biological properties.The relationship between high scaffold porosity and high mechanical properties is contradictory, as it becomes even more complex due to the scaffold degradation process. Biomimetic design has been considered as a viable method to design optimum scaffolds for tissue engineering applications. In this research work, the scaffold designs are based on biomimetic boundary-based bone micro-CT data. Based on the biomimetic boundaries and with the aid of topological optimization schemes, the boundary data and given porosity is used to obtain the initial scaffold designs. In summary, the proposed scaffold design scheme uses the principles of both the boundaries and porosity of the micro-CT data with the aid of numerical optimization and simulation tools.


Assuntos
Materiais Biomiméticos/síntese química , Desenho Assistido por Computador , Desenho de Equipamento/métodos , Engenharia Tecidual/instrumentação , Tecidos Suporte , Materiais Biomiméticos/química , Biomimética/métodos , Osso e Ossos/fisiologia , Simulação por Computador , Humanos , Modelos Anatômicos , Porosidade , Medicina Regenerativa/instrumentação , Medicina Regenerativa/métodos , Resistência ao Cisalhamento , Resistência à Tração , Engenharia Tecidual/métodos , Tecidos Suporte/química , Microtomografia por Raio-X
7.
Methods Mol Biol ; 2147: 19-30, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840807

RESUMO

A new generation of sophisticated tissue engineering scaffolds are developed using the periodicity of trigonometric equations to generate triply periodic minimal surfaces (TPMS). TPMS architectures display minimal surface energy that induce typical pore features and surface curvatures. Here we described a series of TPMS geometries and developed a procedure to build such scaffolds by stereolithography using biocompatible and biodegradable photosensitive resins.


Assuntos
Estereolitografia , Engenharia Tecidual/instrumentação , Tecidos Suporte/química , Implantes Absorvíveis , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Osso e Ossos/fisiologia , Desenho Assistido por Computador , Reagentes para Ligações Cruzadas/química , Humanos , Poliésteres/síntese química , Poliésteres/química , Porosidade , Propriedades de Superfície , Engenharia Tecidual/métodos
8.
Methods Mol Biol ; 2147: 63-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840811

RESUMO

Biofabrication is revolutionizing substitute tissue manufacturing. Skeletal stem cells (SSCs) can be blended with hydrogel biomaterials and printed to form three-dimensional structures that can closely mimic tissues of interest. Our bioink formulation takes into account the potential for cell printing including a bioink nanocomposite that contains low fraction polymeric content to facilitate cell encapsulation and survival, while preserving hydrogel integrity and mechanical properties following extrusion. Clay inclusion to the nanocomposite strengthens the alginate-methylcellulose network providing a biopaste with unique shear-thinning properties that can be easily prepared under sterile conditions. SSCs can be mixed with the clay-based paste, and the resulting bioink can be printed in 3D structures ready for implantation. In this chapter, we provide the methodology for preparation, encapsulation, and printing of SSCs in a unique clay-based bioink.


Assuntos
Bioimpressão/métodos , Regeneração Óssea/fisiologia , Argila/química , Nanocompostos/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Substitutos Ósseos/síntese química , Substitutos Ósseos/química , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Células Cultivadas , Humanos , Tinta , Microtecnologia/métodos , Impressão Tridimensional , Silicatos/química , Células-Tronco/citologia , Células-Tronco/fisiologia , Engenharia Tecidual/instrumentação
9.
Molecules ; 25(24)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371481

RESUMO

The osteogenic differentiation of stem cells is profoundly affected by their microenvironmental conditions. The differentiation behavior of stem cells can be tuned by changing the niche environments. The proteins or peptides that are derived by living organisms facilitate the osteogenic differentiation of stem cells. Here, we have evaluated the osteoinductive and antioxidative potential of the Protaetia brevitarsis seulensis insect-derived protein for human bone marrow-derived mesenchymal stem cells (hBMSCs). The amino acid contents in the isolated protein were determined by an amino acid analyzer. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used to analyze the extract's functional groups and surface morphology. The extracted protein exhibited 51.08% ß-sheet conformation. No adverse effects were observed in extract-treated cells, indicating their biocompatibility. The protein isolate showed an excellent antioxidative property. Besides this, an enhancement in the hBMSCs' mineralization has been observed in the presence of treated protein isolates. Notably, osteogenic marker genes and proteins were effectively expressed in the treated cells. These results indicated that the P. brevitarsis-derived protein isolate can be used as a potential antioxidative biomaterial for bone tissue engineering applications.


Assuntos
Antioxidantes/metabolismo , Besouros/metabolismo , Proteínas de Insetos/metabolismo , Aminoácidos/metabolismo , Animais , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Diferenciação Celular/fisiologia , Linhagem Celular , Humanos , Larva/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Microscopia Eletrônica de Varredura/métodos , Osteogênese/fisiologia , Peptídeos/metabolismo , Conformação Proteica em Folha beta/fisiologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Engenharia Tecidual/métodos
10.
Int J Nanomedicine ; 15: 6945-6960, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061361

RESUMO

Background: Natural clay nanomaterials are an emerging class of biomaterial with great potential for tissue engineering and regenerative medicine applications, most notably for osteogenesis. Materials and Methods: Herein, for the first time, novel tissue engineering scaffolds were prepared by 3D bioprinter using nontoxic and bioactive natural attapulgite (ATP) nanorods as starting materials, with polyvinyl alcohol as binder, and then sintered to obtain final scaffolds. The microscopic morphology and structure of ATP particles and scaffolds were observed by transmission electron microscope and scanning electron microscope. In vitro biocompatibility and osteogenesis with osteogenic precursor cell (hBMSCs) were assayed using MTT method, Live/Dead cell staining, alizarin red staining and RT-PCR. In vivo bone regeneration was evaluated with micro-CT and histology analysis in rat cranium defect model. Results: We successfully printed a novel porous nano-ATP scaffold designed with inner channels with a dimension of 500 µm and wall structures with a thickness of 330 µm. The porosity of current 3D-printed scaffolds ranges from 75% to 82% and the longitudinal compressive strength was up to 4.32±0.52 MPa. We found firstly that nano-ATP scaffolds with excellent biocompatibility for hBMSCscould upregulate the expression of osteogenesis-related genes bmp2 and runx2 and calcium deposits in vitro. Interestingly, micro-CT and histology analysis revealed abundant newly formed bone was observed along the defect margin, even above and within the 3D bioprinted porous ATP scaffolds in a rat cranial defect model. Furthermore, histology analysis demonstrated that bone was formed directly following a process similar to membranous ossification without any intermediate cartilage formation and that many newly formed blood vessels are within the pores of 3D-printed scaffolds at four and eight weeks. Conclusion: These results suggest that the 3D-printed porous nano-ATP scaffolds are promising candidates for bone tissue engineering by osteogenesis and angiogenesis.


Assuntos
Regeneração Óssea/fisiologia , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Osso e Ossos/fisiologia , Cálcio/metabolismo , Chlorocebus aethiops , Condrogênese , Força Compressiva , Regulação da Expressão Gênica , Humanos , Compostos de Magnésio/química , Masculino , Teste de Materiais , Nanotubos/química , Osteogênese/fisiologia , Álcool de Polivinil/química , Porosidade , Impressão Tridimensional , Ratos Sprague-Dawley , Compostos de Silício/química , Células Vero , Microtomografia por Raio-X
11.
PLoS One ; 15(9): e0238115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915812

RESUMO

This work provides an in-depth computational performance study of the parallel finite-difference time-domain (FDTD) method. The parallelization is done at various levels including: shared- (OpenMP) and distributed- (MPI) memory paradigms and vectorization on three different architectures: Intel's Knights Landing, Skylake and ARM's Cavium ThunderX2. This study contributes to prove, in a systematic manner, the well-established claim within the Computational Electromagnetic community, that the main factor limiting FDTD performance, in realistic problems, is the memory bandwidth. Consequently a memory bandwidth threshold can be assessed depending on the problem size in order to attain optimal performance. Finally, the results of this study have been used to optimize the workload balancing of simulation of a bioelectromagnetic problem consisting in the exposure of a human model to a reverberation chamber-like environment.


Assuntos
Algoritmos , Campos Eletromagnéticos , Osso e Ossos/fisiologia , Dispositivos de Armazenamento em Computador , Sistemas Computacionais , Humanos , Rim/fisiologia , Fígado/fisiologia , Modelos Teóricos , Software
12.
Sci Rep ; 10(1): 10955, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616813

RESUMO

Megamammals constituted an important component in the Pleistocene faunal communities of South America. Paleobiological and paleoecological studies involving different megamammal taxa have increased significantly in the last years, but there are still several poorly-known issues of its life history. In this work, we analyze an assemblage composed of 13 individuals of different ontogenetic stages, and possibly different sex, belonging to the giant ground sloth Lestodon armatus (Xenarthra, Folivora), recovered from Playa del Barco site (Pampean Region, Argentina). A dating of 19,849 years Cal BP allows assigning this assemblage to a period of the MIS (Marine Isotope Stage) 2 related to the end of the Last Glacial Maximum. Based on multiple lines of research (e.g. taphonomy, paleopathology, osteohistology, isotopy), we interpret the origin of the assemblage and diverse paleobiological and paleoecological aspects (e.g. social behavior, ontogenetic changes, sexual dimorphism, diseases, resource and habitat use, trophic relationships) of L. armatus. Evidence suggests that the assemblage was formed by a local single event of catastrophic mortality, which affected different members of a social group. This record represents the first accurate evidence of gregariousness for this ground sloth, providing new data on a poorly-known behavior among extinct Folivora.


Assuntos
Osso e Ossos/anatomia & histologia , Osso e Ossos/fisiologia , Cingulados/anatomia & histologia , Cingulados/fisiologia , Ecossistema , Fósseis , Animais , Argentina , Feminino , Masculino
13.
Curr Opin Endocrinol Diabetes Obes ; 27(4): 248-252, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618637

RESUMO

PURPOSE OF REVIEW: An increase in awareness of vegetarian and vegan (plant-based) diets has brought forth numerous studies on their effects on health. The study of nutrition-based factors affecting bone health is difficult, given the length of time before clinical effects are evident. Furthermore, population-based studies must account for strong confounding influences as effects may be because of association, not causality. Yet, it is highly plausible that dietary factors affect bone remodeling in multiple ways. Plant-based diets may alter macronutrient and micronutrient balance, may cause differences in prebiotic and probiotic effects on gut microbiota, and may subtly change the inflammatory and immune response. RECENT FINDINGS: Several recent studies have looked at plant-based nutrition and markers of bone health, using measures such as bone turnover markers, bone mineral density, or fracture rates. Although population based and cross-sectional studies can be prone to confounding effects, a majority did not show differences in bone health between vegetarians/vegans and omnivores as long as calcium and vitamin D intake were adequate. A few prospective cohort or longitudinal studies even demonstrate some benefit to a plant-based diet, but this claim remains unproven. SUMMARY: There is no evidence that a plant-based diet, when carefully chosen to maintain adequate calcium and vitamin D levels, has any detrimental effects on bone health. Theoretical findings suggest a long-term plant-based diet may reduce the risk of osteoporosis, through mechanisms that are currently speculative.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/fisiologia , Dieta Vegana , Dieta Vegetariana , Remodelação Óssea/fisiologia , Cálcio/sangue , Dieta Vegana/efeitos adversos , Dieta Vegana/estatística & dados numéricos , Dieta Vegetariana/efeitos adversos , Dieta Vegetariana/estatística & dados numéricos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Humanos , Estado Nutricional/fisiologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fatores de Risco , Vitamina D/sangue
14.
Arch Osteoporos ; 15(1): 87, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524289

RESUMO

We investigated longitudinal changes in tibia bone strength in master power (jumping and sprinting) and endurance (distance) athletes of both sexes. Bone mass but not cross-sectional moment of inertia was better maintained in power than endurance athletes over time, particularly in men and independent of changes in performance. OBJECTIVE: Assessment of effects of sex and athletic discipline (lower limb power events, e.g. sprint running and jumping versus endurance running events) on longitudinal changes in bone strength in masters athletes. METHODS: We examined tibia and fibula bone properties at distal (4% distal-proximal tibia length) and proximal (66% length) sites using peripheral quantitative computed tomography (pQCT) in seventy-one track and field masters athletes (30 male, 41 female, age at baseline 57.0 ± 12.2 years) in a longitudinal cohort study that included at least two testing sessions over a mean period of 4.2 ± 3.1 years. Effects of time, as well as time × sex and time × discipline interactions on bone parameters and calf muscle cross-sectional area (CSA), were examined. RESULTS: Effects of time were sex and discipline-dependent, even following adjustment for enrolment age, sex and changes in muscle CSA and athletic performance. Male sex and participation in power events was associated with better maintenance of tibia bone mineral content (BMC, an indicator of bone compressive strength) at 4% and 66% sites. In contrast, there was no strong evidence of sex or discipline effects on cross-sectional moment of inertia (CSMI, an indicator of bone bending and torsional strength-P > 0.3 for interactions). Similar sex and discipline-specific changes were also observed in the fibula. CONCLUSIONS: Results suggest that male athletes and those participating in lower limb power-based rather than endurance-based disciplines have better maintenance of bone compressive but not bending and torsional strength.


Assuntos
Envelhecimento , Atletas , Densidade Óssea/fisiologia , Osso e Ossos/fisiologia , Corrida/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Exercício Físico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esportes
15.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(6): 797-803, 2020 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-32538575

RESUMO

Objective: To summarize the active changes of Wnt signaling pathway in osteoarthritis (OA) as well as the influence and mechanism of dual-targeted regulation on cartilage and subchondral bone and the role of crosstalk between them on OA process. Methods: The relevant literature concerning the articular cartilage, subchondral bone, and crosstalk between them in OA and non-OA states by Wnt signaling pathway in vivo and vitro experimental studies and clinical studies in recent years was reviewed, and the mechanism was analyzed and summarized. Results: Wnt signaling can regulate the differentiation and function of chondrocytes and osteoblasts through the classic ß-catenin-dependent or non-classical ß-catenin-independent Wnt signaling pathway and its cross-linking with other signaling pathways, thereby affecting the cartilage and bone metabolism. Moreover, Wnt signaling pathway can activate the downstream protein Wnt1-inducible-signaling pathway protein 1 to regulate the progress of OA and it also can be established gap junctions between different cells in cartilage and subchondral bone to communicate molecules directly to regulate OA occurrence and development. Intra-articular injection of Wnt signaling inhibitor SM04690 can inhibit the progress of OA, and overexpression of Wnt signaling pathway inhibitor Dickkopf in osteoblasts can antagonize the role of vascular endothelial growth factor work on chondrocytes and inhibit the catabolism of its matrix. Conclusion: The regulation of metabolism and function of cartilage and subchondral bone and crosstalk between them is through interactions among Wnt signaling pathway and molecules of other signaling. Therefore, it plays an vital role in the occurrence and development of OA and is expected to become a new target of OA treatment through intervention and regulation of Wnt signaling pathway.


Assuntos
Osso e Ossos , Cartilagem Articular , Osteoartrite , Via de Sinalização Wnt , Osso e Ossos/fisiologia , Cartilagem Articular/fisiologia , Condrócitos/metabolismo , Humanos , Osteoartrite/fisiopatologia , Via de Sinalização Wnt/fisiologia
16.
PLoS One ; 15(6): e0235366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598396

RESUMO

Mechanical loading on bone tissue is an important physiological stimulus that plays a key role in bone growth, fracture repair, and treatment of bone diseases. Osteocytes (bone cells embedded in bone matrix) are well accepted as the sensor cells to mechanical loading and play a critical role in regulating the bone structure in response to mechanical loading. To understand the response of osteocytes to differential mechanical stimulation in physiologically relevant arrangements, there is a need for a platform which can locally stimulate bone cells with different levels of fluid shear stress. In this study, we developed a device aiming to achieve non-contact local mechanical stimulation of osteocytes with a magnetically actuated beam that generates the fluid shear stresses encountered in vivo. The stimulating beam was made from a composite of magnetic powder and polymer, where a magnetic field was used to precisely oscillate the beam in the horizontal plane. The beam is placed above a cell-seeded surface with an estimated gap height of 5 µm. Finite element simulations were performed to quantify the shear stress values and to generate a shear stress map in the region of interest. Osteocytes were seeded on the device and were stimulated while their intracellular calcium responses were quantified and correlated with their position and local shear stress value. We observed that cells closer to the oscillating beam respond earlier compared to cells further away from the local shear stress gradient generated by the oscillating beam. We have demonstrated the capability of our device to mimic the propagation of calcium signalling to osteocytes outside of the stimulatory region. This device will allow for future studies of osteocyte network signalling with a physiologically accurate localized shear stress gradient.


Assuntos
Sinalização do Cálcio , Membrana Celular/metabolismo , Mecanotransdução Celular , Modelos Estatísticos , Osteócitos/citologia , Osteócitos/fisiologia , Estresse Mecânico , Animais , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Camundongos
17.
Am J Nurs ; 120(7): 40-45, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541336

RESUMO

The number of orthopedic surgeries performed in the United States has increased substantially over the past several years. The most recent data available from the Agency for Healthcare Research and Quality indicate that five of the 10 operative procedures most commonly performed during inpatient stays involve the musculoskeletal system. Cigarette smoking is one of the most prevalent and preventable risk factors for musculoskeletal disorders and orthopedic surgery complications. This article discusses the effects of smoking on bone health, the importance of smoking cessation among patients scheduled for or recovering from orthopedic surgery, and the vital role nurses play in supporting patient efforts to lead a tobacco-free life.


Assuntos
Osso e Ossos/fisiologia , Fumar/efeitos adversos , Densidade Óssea , Educação Continuada em Enfermagem , Humanos , Procedimentos Ortopédicos , Estados Unidos , Cicatrização
18.
Sports Health ; 12(5): 431-440, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442050

RESUMO

BACKGROUND: The positive association between physical fitness and bone structure has been widely investigated in children and adolescents, yet no studies have evaluated this influence in young children (ie, preschoolers). HYPOTHESIS: Fit children will present improved bone variables when compared with unfit children, and no sex-based differences will emerge in the sample. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Handgrip strength, standing long jump (SLJ), speed/agility, balance, and cardiorespiratory fitness (CRF) were assessed using the Assessing FITness levels in PREschoolers (PREFIT) test battery in 92 children (50 boys; age range, 3-5 years). A peripheral quantitative computed tomography scan was performed at 38% of the length of the nondominant tibia. Cluster analysis from handgrip strength, SLJ, speed/agility, and CRF was developed to identify fitness groups. Bone variables were compared between sexes and between cluster groups. The association between individual physical fitness components and different bone variables was also tested. RESULTS: Three cluster groups emerged: fit (high values on all included physical fitness variables), strong (high strength values and low speed/agility and CRF), and unfit (low strength, speed/agility, and CRF). The fit group presented higher values than the strong and unfit groups for total and cortical bone mineral content, cortical area, and polar strength strain index (all P < 0.05). The fit group also presented a higher cortical thickness when compared with the unfit group (P < 0.05). Handgrip, SLJ, and speed/agility predicted all bone variables except for total and cortical volumetric bone mineral density. No differences were found for bone variables between sexes. CONCLUSION: The results suggest that global fitness in preschoolers is a key determinant for bone structure and strength but not volumetric bone mineral density. CLINICAL RELEVANCE: Physical fitness is a determinant for tibial bone mineral content, structure, and strength in very young children. Performing physical fitness tests could provide useful information related to bone health in preschoolers.


Assuntos
Osso e Ossos/anatomia & histologia , Osso e Ossos/fisiologia , Aptidão Física/fisiologia , Caracteres Sexuais , Densidade Óssea/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Teste de Esforço/métodos , Feminino , Força da Mão/fisiologia , Humanos , Extremidade Inferior/fisiologia , Masculino , Estudos Retrospectivos , Tíbia/fisiologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-32397137

RESUMO

Background: Mechanisms that influence muscle strength can interfere with neuromotor performance and overall health, thus hormone markers and maturation can interact in this process. Objective: The present study aimed to verify the relationship of hormonal markers and biological maturation on neuromotor abilities in young people. Methods: This is a cross-sectional study with 44 female participants (11.5 ± 1.5 years). Hormones were analyzed biochemically. Skeletal and somatic maturation were analyzed using anthropometry. The muscular power of the upper and lower limbs, body speed with change of direction, and speed of the upper limbs were verified. Results: Bone age was correlated with hormonal markers (estradiol: r = 0.58; p = 0.0007), (testosterone: r = 0.51; p = 0.005). Peak growth velocity correlated with estradiol (r = 0.51; p = 0.004). The power of the lower limbs (estradiol: r = 0.52; p = 0.006; testosterone: r = 0.42; p = 0.03) and of the upper limbs (estradiol: r = 0.51; p = 0.007; testosterone: r = 0.42; p = 0.02) had a positive correlation with hormone levels and had similar results with maturation. The analysis by artificial neural networks indicated that the maturation can predict the neuromotor performance between 57.4% and 76%, while the hormonal markers showed a potential of more than 95% for the foreshadowing of the neuromotor performance of the upper limbs. Conclusion: It was possible to conclude that the hormones had a relationship with maturational development and bone age in female subjects.


Assuntos
Envelhecimento , Estradiol , Destreza Motora , Testosterona , Adolescente , Biomarcadores/sangue , Osso e Ossos/fisiologia , Criança , Estudos Transversais , Estradiol/sangue , Feminino , Humanos , Força Muscular , Redes Neurais de Computação , Testosterona/sangue
20.
Eur J Endocrinol ; 183(2): 181-189, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454455

RESUMO

Objective: Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design: Prospective cohort study. Methods: Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. Conclusions: In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.


Assuntos
Antagonistas de Androgênios/farmacologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Calcificação Fisiológica/efeitos dos fármacos , Acetato de Ciproterona/farmacologia , Adulto , Idoso , Bélgica , Remodelação Óssea/efeitos dos fármacos , Cálcio/sangue , Estudos de Coortes , Homeostase/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Estudos Prospectivos , Delitos Sexuais , Testosterona/sangue
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