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1.
Am J Orthod Dentofacial Orthop ; 158(3): 383-390, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32732004

RESUMO

INTRODUCTION: Our aim was to analyze the correlation between growth status in height and chronological age, carpal maturation, cervical maturation, and dental maturation, and assess the diagnostic performance of Demirjian's dental maturation as an indicator of the pubertal growth spurt, through a retrospective longitudinal study. METHODS: Records of 60 Canadian patients obtained from the Burlington Growth Centre, which included height and weight charts and a set of x-rays at 6 points in time, were analyzed. The images at each point in time included 1 hand and wrist radiograph, a lateral cephalometric x-ray, and one 45° oblique cephalometric radiograph of each side, which were analyzed using the methods of Fishman, Baccetti, and Demirjian on the mandibular left and right second molars, respectively. The onset of the pubertal growth peak in height (distance to growth peak [DGP]) was identified, and the correlation between methods with DGP was assessed. RESULTS: High levels of correlation were obtained between the methods of Fishman, Baccetti, and Demirjian with DGP. The cutoff point between prepubertal and postpubertal stages was F stage for women and G stage for men, with statistically significant levels of sensitivity and specificity for the test. CONCLUSIONS: The use of the method of Demirjian applied to mandibular second molars is plausible as a predictor of the occurrence of the DGP for the studied population.


Assuntos
Determinação da Idade pelo Esqueleto , Calcificação de Dente , Desenvolvimento Ósseo , Canadá , Feminino , Humanos , Estudos Longitudinais , Masculino , Dente Molar , Estudos Retrospectivos
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(3): 308-314, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32762161

RESUMO

ObjectiveTo evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). MethodSeventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. ResultsHV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( P < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( t=2.78 and 2.20, all P < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( P>0.05), and both were higher than that in no intervention group (162±4 cm, P < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. ConclusionsLong term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.


Assuntos
Letrozol/uso terapêutico , Adolescente , Estatura , Desenvolvimento Ósseo , Criança , Hormônio Liberador de Gonadotropina , Transtornos do Crescimento , Humanos , Masculino
3.
Adv Exp Med Biol ; 1262: 183-202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32613584

RESUMO

This chapter presents a methodological framework which could be used to produce accurate anatomical 3D models and animations of the developing skull, with a focus on the temporal bone. Initial modelling is based on information from core texts and visual references, before optimising these models for use in interactive real-time applications. A series of 3D modelling and animation workflows typically used in computer games and animation industry were tested and compared. Workflows most suitable for the production of a 3D visualisation of the developing temporal bone were documented in detail and used to produce the final 3D models. 3D models of the developing temporal bone were then implemented in an interactive mobile application, which allowed users to explore the 3D models on their Android mobile device and use augmented reality to enhance real-world information. Results of tests conducted in this research suggest that 3D modelling workflows which mimic the processes occurring during development of the temporal bone are most suitable for producing realistic 3D models. Animation workflows tested in this research have all shown potential to produce morphing animations of the developing temporal bone. The significant time required to create deformation setups and animations themselves however suggests that using scripting to automate these workflows would increase their usability in projects with a limited timeframe.


Assuntos
Desenvolvimento Ósseo , Modelos Anatômicos , Osteologia , Osso Temporal , Humanos , Imageamento Tridimensional , Aplicativos Móveis/normas , Osteologia/educação , Materiais de Ensino/normas , Osso Temporal/crescimento & desenvolvimento
4.
PLoS Genet ; 16(7): e1008884, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639996

RESUMO

The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ankank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate excretion via the urine was substantially reduced in Ankank/ank mice. Citrate was even undetectable in the urine of a human patient lacking functional ANKH. The hydroxyapatite of Ankank/ank mice contained dramatically reduced levels of both, citrate and PPi and displayed diminished strength. Our results show that ANKH is a critical contributor to extracellular citrate and PPi homeostasis and profoundly affects bone matrix composition and, consequently, bone quality.


Assuntos
Osso e Ossos/metabolismo , Calcinose/genética , Ácido Cítrico/metabolismo , Proteínas de Transporte de Fosfato/genética , Trifosfato de Adenosina/metabolismo , Animais , Desenvolvimento Ósseo/genética , Calcinose/metabolismo , Calcinose/patologia , Diferenciação Celular , Células Cultivadas , Difosfatos/metabolismo , Humanos , Fenômenos Mecânicos , Camundongos , Mutação/genética , Proteínas de Transporte de Fosfato/metabolismo
5.
PLoS One ; 15(6): e0233377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502155

RESUMO

The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL's peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.


Assuntos
Desenvolvimento Ósseo/genética , Ossos Faciais/anatomia & histologia , Desenvolvimento Maxilofacial/genética , Alelos , Animais , Osso e Ossos/anatomia & histologia , Mapeamento Cromossômico/métodos , Camundongos de Cruzamento Colaborativo/genética , Face/anatomia & histologia , Feminino , Variação Genética/genética , Genótipo , Masculino , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
6.
Unfallchirurg ; 123(8): 607-615, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32444884

RESUMO

BACKGROUND: Inflammatory rheumatic diseases in childhood and adolescence are a special challenge in the treatment of acute trauma. The pharmaceutical treatment strategies for children and adolescents have been modified. OBJECTIVE: Which special aspects must be considered in young patients suffering from rheumatism when a trauma necessitates an operative procedure? MATERIAL AND METHOD: A literature search was carried out to elaborate recommendations for the practice. RESULTS: The joint-related alterations in young patients suffering from rheumatism differ with respect to the differently altered inflammatory rheumatic destruction. The extent of these inflammatory destructive alterations dictates the operative approach. Consequences arise in paying attention to the concurrent medication with respect to avoidance of events triggering an exacerbation and tissue infections. The bone strength necessitates an individualized selection of implants and sometimes influences the duration of follow-up treatment. In the early stages of the inflammatory process the approach in cases of trauma is no different to that for healthy patients but in later stages (Larsen stage III) it does differ. CONCLUSION: An interdisciplinary concept can help to avoid disadvantages in the treatment of the underlying disease. Due to the special dysplastic anatomy and tissue alterations, trauma in these patients is a particular challenge.


Assuntos
Fraturas Ósseas , Doenças Reumáticas , Adolescente , Desenvolvimento Ósseo , Criança , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/terapia , Humanos , Doenças Reumáticas/complicações , Risco
7.
BMC Med Genet ; 21(1): 64, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228492

RESUMO

BACKGROUND: The calcium-selective channel TRPV6 (transient receptor potential cation channel subfamily V member 6) is crucial for maternal-fetal calcium transport across the placenta. TRPV6 mutations have recently been associated with an antenatally severe under-mineralising skeletal dysplasia accompanied by postnatal biochemical abnormalities. This is the first post-mortem report in a patient with TRPV6 skeletal dysplasia. CASE PRESENTATION: The female infant had severe antenatal and postnatal skeletal abnormalities by 20 weeks gestation and was ventilator-dependent from birth. These skeletal abnormalities were apparent at an earlier gestational age than in previous reported cases and a more severe clinical course ensued. Biochemical and skeletal abnormalities, including bone density, improved postnatally but cardiac arrest at 4 months of age led to withdrawal of intensive care. Compound heterozygous TRPV6 variants (c.1978G > C p.(Gly660Arg) and c.1528C > T p.(Arg510Ter)) were identified on exome sequencing. Post-mortem identified skeletal abnormalities but no specific abnormalities in other organ systems. No placental pathology was found, multi-organ histological features reflected prolonged intensive care only. Post-mortem macroscopic examination indicated reduced thoracic size and short, pale and pliable ribs. Histological examination identified reduced number of trabeculae in the diaphyses (away from the growth plates), whereas metaphyses showed adequate mineralisation and normal number of trabeculae, but with slightly enlarged reactive chondrocytes, indicating post-natal skeletal growth recovery. Post-mortem radiological findings demonstrated improved bone density, improved rib width, healed fractures, although ribs were still shorter than normal. Long bones (especially humerus and femur) had improved from initial poorly defined metaphyses and reduced bone density to sharply defined metaphyses, prominent growth restart lines in distal diaphyses and bone-in-bone appearance along diaphyses. CONCLUSIONS: This case provide bone histological confirmation that human skeletal development is compromised in the presence of TRPV6 pathogenic variants. Post-mortem findings were consistent with abnormal in utero skeletal mineralisation due to severe calcium deficit from compromised placental calcium transfer, followed by subsequent phenotypic improvement with adequate postnatal calcium availability. Significant skeletal recovery occurs in the early weeks of postnatal life in TRPV6 skeletal dysplasia.


Assuntos
Desenvolvimento Ósseo , Osso e Ossos/patologia , Canais de Cálcio/genética , Desenvolvimento Infantil/fisiologia , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Canais de Cátion TRPV/genética , Autopsia , Desenvolvimento Ósseo/genética , Osso e Ossos/anormalidades , Calcificação Fisiológica/genética , Cálcio/metabolismo , Canais de Cálcio/análise , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Osteocondrodisplasias/reabilitação , Parto/fisiologia , Canais de Cátion TRPV/análise
8.
Life Sci ; 253: 117636, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251631

RESUMO

BMAL1 is a core component of the circadian clock loop, which directs the sophisticated circadian expression of clock-controlled genes. Skeletal Bone development is a complex biological process involving intramembranous ossification, endochondral ossification and bone remodeling, as well as specific cells, such as mesenchymal cells, osteoblasts, osteoclasts, chondrocytes, etc. Growing evidences suggest that BMAL1 is indispensable for hard tissue development, including bone, cartilage and teeth. Loss of BMAL1 in animals can inhibit bone and cartilage development, and result in abnormal bone mass. In mesenchymal cells, BMAL1 defect inhibits osteoblastic and chondrocytic differentiation. Inactivation of BMAL1 also can promote the differentiation and formation of osteoclasts and increase bone resorption. Specifically, preclinical data demonstrate that the abnormity of BMAL1 expression is associated with skeletal disorders such as skeletal mandibular hypoplasia, osteoarthritis, osteoporosis, etc. In this review, we systemically describe the impact of BMAL1 in skeletal development and homeostasis, and devote to searching new therapy strategies for bone disorders.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Desenvolvimento Ósseo/efeitos dos fármacos , Fatores de Transcrição ARNTL/genética , Animais , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Diferenciação Celular , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Relógios Circadianos/genética , Regulação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese , Dente/metabolismo
10.
Lancet Child Adolesc Health ; 4(4): 281-289, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32119840

RESUMO

BACKGROUND: Hutchinson-Gilford progeria syndrome (termed progeria in this Article) is a rare sporadic genetic disorder. One early clinical manifestation of progeria is abnormal skeletal growth, yet this growth has not been fully characterised. We aimed to characterise the skeletal maturation and long-bone growth patterns of patients with the clinical phenotype of progeria. METHODS: For this retrospective study, we reviewed skeletal surveys of patients (aged <20 years) with progeria obtained over a 9·5-year period. Most surveys included radiographs of the hands and long bones (humeri, radii, ulnas, tibias, and fibulas). Bone ages of these patients were estimated by the standards of Greulich and Pyle. Following the established methods for studying long-bone growth, the study cohort was separated into two overlapping age groups: longitudinal bone length measurements were made between physes for the childhood group (aged 12 years or younger) and from the upper margins of the proximal to the lower margin of the distal ossified epiphyses for the adolescent group (aged 10 years or older). Bone age estimates and bone length measurements were plotted against the chronological age of patients and compared with reference standards. Statistical analyses were based on mixed models. FINDINGS: 85 patients with progeria and 250 skeletal surveys were included in our study. For both sexes, bone age estimates showed a more advanced skeletal maturation rate throughout all chronological ages than the normal rate of 1 (p<0·0001), with the rate of maturation being 1·09 (SE 0·02) for boys and 1·14 (0·02) for girls. Longitudinal long-bone lengths began to deviate from normal standards by age 1-2 years. Growth curves for these long bones plateaued at about half the normal eventual bone length, and the half-life (the time taken to grow to half the eventual bone length) was also about half the time compared with normal standards. INTERPRETATION: Our study established growth curves that might serve as reference standards for skeletal maturation and long-bone growth of patients with the clinical phenotype of progeria. FUNDING: The Progeria Research Foundation, the US National Heart, Lung and Blood Institute, the Dana-Farber Cancer Institute Stop&Shop Pediatric Brain Tumor Program, the US National Center for Research Resources, US National Institutes of Health.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Desenvolvimento Ósseo/genética , Progéria/genética , Adolescente , Algoritmos , Desenvolvimento Ósseo/fisiologia , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Humanos , Lactente , Masculino , Fenótipo , Progéria/diagnóstico por imagem , Progéria/epidemiologia , Progéria/patologia , Radiografia/métodos , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
11.
PLoS One ; 15(3): e0230240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32187215

RESUMO

It has been demonstrated in numerous studies that bee pollen supplementation shows numerous positive effects on health. However, its impact on bones is largely unknown. The purpose of this study was to investigate the effect of bee pollen supplementation on the tibia biomechanical properties and bone morphometric measures using Japanese quail as an animal model. The experiment was arranged in a 2x2x2 factorial design, with sex, quail line (meat-type or egg-lying type), and bee pollen inclusion (0 or 10 g/kg of feed) as factors. The quails were one-day-old at the beginning of the experiment, they were euthanized after 42 days. Our study showed for the first time unfavorable effects of bee pollen on bones properties. Bee pollen supplementation negatively affected bone structure, irrespective of quails' sex or line type. Bone length (P < 0.001), weight (P < 0.01), and mean relative wall thickness (P < 0.01) and mineralization (P < 0.05) were reduced by bee pollen treatment. For female quails, irrespective of line type, the decrease of yield load (P < 0.001), ultimate load (P < 0.01), yield stress (P < 0.001) and ultimate stress (P < 0.05) was noted. Analysis of growth plate in bone metaphysis showed that bee pollen supplementation slowed the process of bone maturation irrespective of sex (P < 0.05). On contrary, dietary bee pollen positively affected bone homeostasis of trabecular bone in bone metaphysis as bone mineral density increased in experimental groups (P < 0.05). In males, this was the result of the increase of trabecular thickness (P < 0.01), in females due to the reduction of trabecular space (P < 0.001). In conclusion, our results demonstrate that bee pollen (1.0%, 10 g/kg of feed) supplementation caused significant negative effects on the mechanical endurance of the tibia of quails, while showed beneficial effects on trabecular bone histomorphometry.


Assuntos
Abelhas/metabolismo , Densidade Óssea/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Pólen/metabolismo , Tíbia/efeitos dos fármacos , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Coturnix , Dieta , Suplementos Nutricionais , Feminino , Masculino , Carne , Codorniz
12.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R929-R939, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32130027

RESUMO

Women in low- and middle-income countries frequently consume a protein-deficient diet during pregnancy and breastfeeding. The effects of gestational malnutrition on fetal and early postnatal development can have lasting adverse effects on offspring metabolism. Expanding on previous studies in rodent models, we utilized a nonhuman primate model of gestational and early-life protein restriction (PR) to evaluate effects on the organ development and glucose metabolism of juvenile offspring. Offspring were born to dams that had consumed a control diet containing 26% protein or a PR diet containing 13% protein. Offspring were maintained on the PR diet and studied [body and serum measurements, intravenous glucose tolerance tests (ivGTTs), and dual-energy X-ray absorptiometry scans] up to 7 mo of age, at which time tissues were collected for analysis. PR offspring had age-appropriate body weight and were euglycemic but exhibited elevated fasting insulin and reduced initial, but increased total, insulin secretion during an ivGTT at 6 mo of age. No changes were detected in pancreatic islets of PR juveniles; however, PR did induce changes, including reduced kidney size, and changes in liver, adipose tissue, and muscle gene expression in other peripheral organs. Serum osteocalcin was elevated and bone mineral content and density were reduced in PR juveniles, indicating a significant impact of PR on early postnatal bone development.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Dieta com Restrição de Proteínas , Metabolismo Energético , Retardo do Crescimento Fetal/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Animais , Glicemia/metabolismo , Composição Corporal , Desenvolvimento Ósseo , Modelos Animais de Doenças , Metabolismo Energético/genética , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/fisiopatologia , Regulação da Expressão Gênica no Desenvolvimento , Resistência à Insulina , Macaca mulatta , Masculino , Estado Nutricional , Gravidez
13.
Gene ; 743: 144511, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112984

RESUMO

Valgus-varus Deformity (VVD) is an outward or inward deviation of the tibiotarsus or tarsometatarsus, which results in physical distress of chickens and economic loss in poultry industry. While the etiology and pathogenesis of VVD at the molecular level are still not fully understood so far. Here, based on a case/control design with VVD birds and normal birds, we identified genes and lncRNAs which associated with VVD using RNA sequencing. Transcriptome analysis revealed 231 differentially expressed mRNAs and 23 differentially expressed lncRNAs between case and control of leg cartilage. We identified the cis- and trans-regulatory targets of the differentially expressed lncRNAs, and we constructed a functional lncRNA-mRNA co-expression network. Analysis of the network showed that the differentially expressed mRNAs and the target genes of the differentially expressed lncRNAs were enriched in the signaling pathways associated with bone development, including p53, MAPK, Toll-like receptor, Jak-STAT, Hedgehog, and PPAR. The expression levels of DENND4A, FGF10, FGF12 and BMP3 were also determined in cartilage and other six tissues. Overall, our study predicted the mRNAs and lncRNAs related with leg diseases by transcriptome analyses, which might contribute to understand the etiology and pathogenesis of VVD. It established the foundation for the further research on the function of -mRNAs and lncRNAs in skeleton development.


Assuntos
Mau Alinhamento Ósseo/veterinária , Galinhas/genética , Deformidades Congênitas das Extremidades Inferiores/veterinária , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Animais , Desenvolvimento Ósseo/genética , Mau Alinhamento Ósseo/genética , Estudos de Casos e Controles , Galinhas/anormalidades , Fator 10 de Crescimento de Fibroblastos/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Ensaios de Triagem em Larga Escala , Extremidade Inferior/crescimento & desenvolvimento , Deformidades Congênitas das Extremidades Inferiores/genética
16.
Poult Sci ; 99(2): 734-743, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029158

RESUMO

In poultry production, vaccination is an effective measure to protect chickens from diseases. Vaccination, however, is a stressor that may induce stress responses that interfere with the growth and development of chickens. The interaction between the skeletal and immune systems on bone quality has gained more attention. In the present study, the influence of high frequency vaccinations on the bone development of layer pullets was investigated. Thirty 35-day-old SPF White Leghorn layer pullets were obtained and randomly subjected to the following treatments: vaccinated against Newcastle disease (ND) with LoSota vaccine once at 35-day-old (V1, control); 4 times at 35, 49, 63, and 77 d of age (V4); and 7 times at 35, 42, 49, 56, 63, 70, and 77 d of age (V7). The body weight and organ index of the spleen, thymus, and tibia were recorded. The antibody titer and serum and the tibia calcium and phosphorus concentrations were measured. The transcription levels of the IL-6, IL-17, TNF-α, receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) genes were determined in spleen, thymus, and the tibia. The results showed that V7 decreased body weight and increased the ND antibody titer, compared to V1-chickens. The expression levels of IL-6, IL-17, and TNF-α were upregulated in spleen, thymus, and the tibia of V7 chickens. In the tibia, RANKL was upregulated, while OPG was downregulated by V7 treatment. The results indicate that high frequency vaccination induces immune stress and impairs bone development. The results suggest that the augmented cytokine expression in immune organs and the tibia is associated with activation of the OPG/RANKL pathway, which, in turn, enhances osteoclastogenesis. The appropriate frequency of vaccination should support optimal bone development and full immunoprotection in layer pullets.


Assuntos
Desenvolvimento Ósseo/fisiologia , Galinhas/fisiologia , Osteogênese , Estresse Fisiológico/imunologia , Vacinação/veterinária , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Desenvolvimento Ósseo/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Feminino , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Transdução de Sinais/efeitos dos fármacos , Organismos Livres de Patógenos Específicos , Tíbia/efeitos dos fármacos , Tíbia/metabolismo
17.
Mol Cells ; 43(2): 168-175, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-31896233

RESUMO

Runx2 is an essential transcription factor for skeletal development. It is expressed in multipotent mesenchymal cells, osteoblast-lineage cells, and chondrocytes. Runx2 plays a major role in chondrocyte maturation, and Runx3 is partly involved. Runx2 regulates chondrocyte proliferation by directly regulating Ihh expression. It also determines whether chondrocytes become those that form transient cartilage or permanent cartilage, and functions in the pathogenesis of osteoarthritis. Runx2 is essential for osteoblast differentiation and is required for the proliferation of osteoprogenitors. Ihh is required for Runx2 expression in osteoprogenitors, and hedgehog signaling and Runx2 induce the differentiation of osteoprogenitors to preosteoblasts in endochondral bone. Runx2 induces Sp7 expression, and Runx2, Sp7, and canonical Wnt signaling are required for the differentiation of preosteoblasts to immature osteoblasts. It also induces the proliferation of osteoprogenitors by directly regulating the expression of Fgfr2 and Fgfr3. Furthermore, Runx2 induces the proliferation of mesenchymal cells and their commitment into osteoblast-lineage cells through the induction of hedgehog (Gli1, Ptch1, Ihh), Fgf (Fgfr2, Fgfr3), Wnt (Tcf7, Wnt10b), and Pthlh (Pth1r) signaling pathway gene expression in calvaria, and more than a half-dosage of Runx2 is required for their expression. This is a major cause of cleidocranial dysplasia, which is caused by heterozygous mutation of RUNX2. Cbfb, which is a co-transcription factor that forms a heterodimer with Runx2, enhances DNA binding of Runx2 and stabilizes Runx2 protein by inhibiting its ubiquitination. Thus, Runx2/Cbfb regulates the proliferation and differentiation of chondrocytes and osteoblast-lineage cells by activating multiple signaling pathways and via their reciprocal regulation.


Assuntos
Desenvolvimento Ósseo/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Humanos
18.
Commun Biol ; 3(1): 45, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988398

RESUMO

Intraflagellar transport (IFT) proteins are essential for cilia assembly and function. IFT protein mutations lead to ciliopathies, which manifest as variable skeletal abnormalities. However, how IFT proteins regulate cell alignment during bone development is unknown. Here, we show that the deletion of IFT20 in osteoblast lineage using Osterix-Cre and inducible type I Collagen-CreERT cause a compromised cell alignment and a reduced bone mass. This finding was validated by the disorganized collagen fibrils and decreased bone strength and stiffness in IFT20-deficient femurs. IFT20 maintains cilia and cell alignment in osteoblasts, as the concentric organization of three-dimensional spheroids was disrupted by IFT20 deletion. Mechanistically, IFT20 interacts with the ceramide-PKCζ complex to promote PKCζ phosphorylation in cilia and induce the apical localization of ß-catenin in osteoblasts, both of which were disrupted in the absence of IFT20. These results reveal that IFT20 regulates polarity and cell alignment via ceramide-pPKCζ-ß-catenin signaling during bone development.


Assuntos
Desenvolvimento Ósseo/genética , Proteínas de Transporte/metabolismo , Ceramidas/metabolismo , Cílios/metabolismo , Osteócitos/metabolismo , Proteína Quinase C/metabolismo , beta Catenina/metabolismo , Animais , Proteínas de Transporte/genética , Diferenciação Celular/genética , Linhagem da Célula , Polaridade Celular/genética , Fêmur/metabolismo , Camundongos Transgênicos , Fosforilação/genética , Proteína cdc42 de Ligação ao GTP/metabolismo
20.
Acta Paediatr ; 109(1): 208, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31194260
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