Fracturas del extremo distal del radio en el esqueleto inmaduro: estudio epidemiológico en el Centro Hospitalario Pereira Rossell / Fraturas da extremidade distal do rádio no esqueleto imaturo: estudo epidemiológico no Hospital Pereira Rossell / Fracture of the distal end of the radius in children: epidemiological study at the Pereira Rossell Hospital Center

Objetivo principal: Conocer la epidemiologia de las fracturas del cuarto distal del radio en el esqueleto en crecimiento y el tratamiento realizado en el CHPR en los años 2017 y 2018. Objetivos específicos: Valorar re-desplazamiento, necesidad de re manipulación, complicaciones, re-fractura. Metodología: Estudio observacional descriptivo retrospectivo. Criterios de inclusión: pacientes de 0 a 14 años con fractura de radio distal (fisaria, metafisaria y suprametafisaria) valorados en el CHPR entre 1 enero del 2017 y 31 diciembre del 2018. Criterios de exclusión: pacientes con radiografía normal, fracturas en miembros con malformaciones, infecciones óseas, patología tumoral maligna o benigna. Obtención de datos: Valoración de radiografías de puño y antebrazo realizadas en el CHPR en 2017 y 18, iniciales y evolutivas. Se analizaron: edad, sexo, fecha fractura, topografía de la fractura, desplazamiento inicial, tratamiento, evolución radiográfica y complicaciones. Resultados: se incluyeron 662 pacientes. Siendo en su mayoría de género masculino (65%), con una media de 9 años, miembro derecho (61%), en los meses de verano (36%). En cuanto a la topografía se evidenció una frecuencia mayor en fracturas tipo rodete y metafisarias (31.72% y 31.57%), seguido por suprametafisaria (18.43%) y fisaria (18.28%). El tratamiento realizado fue ortopédico en el 86.56% de los casos, mientras que quirúrgico fue el 12.84%, en su gran mayoría con alambres de Kirschner (11,2%). El tiempo de inmovilización promedio fue de 6 semanas, con un porcentaje de complicaciones del 14.05% del total de las fracturas. Conclusiones: Se valoraron las características de los pacientes y fracturas de radio distal en el CHPR en los años 2017 y 18, siendo un total de 662 fracturas, en las que su mayoría se realizó tratamiento ortopédico con un índice de complicaciones que ronda el 14%, siendo mayor cuanto mayor es el desplazamiento inicial de la fractura.

Objetivo principal: Conhecer a epidemiologia das fraturas do quarto distal do rádio no esqueleto em crescimento e o tratamento realizado no CHPR nos anos de 2017 e 2018. Objetivos específicos: Avaliar re-deslocamento, necessidade de remanipulação, complicações, refratura. Metodologia: Estudo observacional descritivo retrospectivo. Critérios de inclusão: pacientes de 0 a 14 anos com fratura do rádio distal (fisário, metafisário e suprametafisário) avaliados no CHPR entre 1º de janeiro de 2017 e 31 de dezembro de 2018. Critérios de exclusão: pacientes com radiografias normais, fraturas em membros com malformações, osso infecções, patologia tumoral maligna ou benigna. Coleta de dados: Avaliação das radiografias de punho e antebraço realizadas no CHPR em 2017 e 18, inicial e evolutiva. Foram analisados: idade, sexo, data da fratura, topografia da fratura, deslocamento inicial, tratamento, evolução radiográfica e complicações. Resultados: 662 pacientes foram incluídos. Sendo maioritariamente do sexo masculino (65%), com média de 9 anos, membro direito (61%), nos meses de verão (36%). Em relação à topografia, foi evidenciada maior frequência nas fraturas da borda e metafisárias (31,72% e 31,57%), seguidas das suprametafisárias (18.43%) e fisárias (18.28%). O tratamento realizado foi ortopédico em 86.56% dos casos, enquanto cirúrgico em 12.84%, sendo a maioria com fios de Kirschner (11,2%). O tempo médio de imobilização foi de 6 semanas, com percentual de complicações de 14.05%. Conclusões: Foram avaliadas as características dos pacientes e fraturas do rádio distal no CHPR nos anos de 2017 e 18, com um total de 662 fraturas (0,9 por dia), em que a maioria foi submetida a tratamento ortopédico com índice de complicações que fica em torno de 14%, sendo maior quanto maior for o deslocamento inicial da fratura.

Title: Fractures of the distal end of the radius in the immature skeleton. Epidemiological study at the Pereira Rossell Hospital Center. Main objective: To know the epidemiology of fractures of the distal fourth of the radius in the growing skeleton and the treatment carried out in the CHPR in the years 2017 and 2018. Specific objectives: To assess re-displacement, need for re-manipulation, complications, re- fracture. Methodology: Retrospective descriptive observational study. Inclusion criteria: patients aged 0 to 14 years with distal radius fracture (physeal, metaphyseal and suprametaphyseal) evaluated at the CHPR between January 1, 2017 and December 31, 2018. Exclusion criteria: patients with normal radiographs, fractures in limbs with malformations, bone infections, malignant or benign tumor pathology. Data collection: Assessment of fist and forearm X-rays performed at the CHPR in 2017 and 18, initial and evolutionary. The following were analyzed: age, sex, fracture date, fracture topography, initial displacement, treatment, radiographic evolution and complications. Results: 662 patients were included. Being mostly male (65%), with an average of 9 years, right limb (61%), in the summer months (36%). Regarding the topography, a higher frequency was evidenced in rim and metaphyseal fractures (31.72% and 31.57%), followed by suprametaphyseal (18.43%) and physeal (18.28%). The treatment performed was orthopedic in 86.56% of the cases, while surgical was 12.84%, mostly with Kirschner wires (11.2%). The average immobilization time was 6 weeks, with a percentage of complications of 14.05%. Conclusions: The characteristics of the patients and fractures of the distal radius in the CHPR in the years 2017 and 18 were evaluated, with a total of 662 fractures (0.9 per day), in which the majority underwent orthopedic treatment with an index of complications that is around 14%, being greater the greater the initial displacement of the fracture.

Primary cilia in skeletal development and disease.

Primary cilia are non-motile, microtubule-based sensory organelle present in most vertebrate cells with a fundamental role in the modulation of organismal development, morphogenesis, and repair. Here we focus on the role of primary cilia in embryonic and postnatal skeletal development. We examine evidence supporting its involvement in physiochemical and developmental signaling that regulates proliferation, patterning, differentiation and homeostasis of osteoblasts, chondrocytes, and their progenitor cells in the skeleton. We discuss how signaling effectors in mechanotransduction and bone development, such as Hedgehog, Wnt, Fibroblast growth factor and second messenger pathways operate at least in part at the primary cilium. The relevance of primary cilia in bone formation and maintenance is underscored by a growing list of rare genetic skeletal ciliopathies. We collate these findings and summarize the current understanding of molecular factors and mechanisms governing primary ciliogenesis and ciliary function in skeletal development and disease.

The genetic architecture and evolution of the human skeletal form.

The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221 x-rays from the UK Biobank to extract a comprehensive set of SPs, which were associated with 145 independent loci genome-wide. Structural equation modeling suggested that limb proportions exhibited strong genetic sharing but were independent of width and torso proportions. Polygenic score analysis identified specific associations between osteoarthritis and hip and knee SPs. In contrast to other traits, SP loci were enriched in human accelerated regions and in regulatory elements of genes that are differentially expressed between humans and great apes. Combined, our work identifies specific genetic variants that affect the skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.

A single-cell census of mouse limb development identifies complex spatiotemporal dynamics of skeleton formation.

Limb development has long served as a model system for coordinated spatial patterning of progenitor cells. Here, we identify a population of naive limb progenitors and show that they differentiate progressively to form the skeleton in a complex, non-consecutive, three-dimensional pattern. Single-cell RNA sequencing of the developing mouse forelimb identified three progenitor states: naive, proximal, and autopodial, as well as Msx1 as a marker for the naive progenitors. In vivo lineage tracing confirmed this role and localized the naive progenitors to the outer margin of the limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that the progressive transition of Msx1+ naive progenitors into proximal and autopodial progenitors coincides with their differentiation to Sox9+ chondroprogenitors, which occurs along all the forming skeletal segments. Indeed, tracking the spatiotemporal sequence of differentiation showed that the skeleton forms progressively in a complex pattern. These findings suggest an alternative model for limb skeleton development.

Postnatal development in a marsupial model, the fat-tailed dunnart (Sminthopsis crassicaudata; Dasyuromorphia: Dasyuridae).

Marsupials exhibit unique biological features that provide fascinating insights into many aspects of mammalian development. These include their distinctive mode of reproduction, altricial stage at birth, and the associated heterochrony that is required for their crawl to the pouch and teat attachment. Marsupials are also an invaluable resource for mammalian comparative biology, forming a distinct lineage from the extant placental and egg-laying monotreme mammals. Despite their unique biology, marsupial resources are lagging behind those available for placentals. The fat-tailed dunnart (Sminthopsis crassicaudata) is a laboratory based marsupial model, with simple and robust husbandry requirements and a short reproductive cycle making it amenable to experimental manipulations. Here we present a detailed staging series for the fat-tailed dunnart, focusing on their accelerated development of the forelimbs and jaws. This study provides the first skeletal developmental series on S. crassicaudata and provides a fundamental resource for future studies exploring mammalian diversification, development and evolution.

An atlas of seven zebrafish hox cluster mutants provides insights into sub/neofunctionalization of vertebrate Hox clusters.

Vertebrate Hox clusters are comprised of multiple Hox genes that control morphology and developmental timing along multiple body axes. Although results of genetic analyses using Hox-knockout mice have been accumulating, genetic studies in other vertebrates have not been sufficient for functional comparisons of vertebrate Hox genes. In this study, we isolated all of the seven hox cluster loss-of-function alleles in zebrafish using the CRISPR-Cas9 system. Comprehensive analysis of the embryonic phenotype and X-ray micro-computed tomography scan analysis of adult fish revealed several species-specific functional contributions of homologous Hox clusters along the appendicular axis, whereas important shared general principles were also confirmed, as exemplified by serial anterior vertebral transformations along the main body axis, observed in fish for the first time. Our results provide insights into discrete sub/neofunctionalization of vertebrate Hox clusters after quadruplication of the ancient Hox cluster. This set of seven complete hox cluster loss-of-function alleles provide a formidable resource for future developmental genetic analysis of the Hox patterning system in zebrafish.

Fracturas metafisarias de radio distal desplazadas en el esqueleto en crecimiento: ¿cuál es el mejor método terapéutico? revisión bibliográfica sistematizada / Displaced distal radius metaphyseal fractures in the growing skeleton: what is the best therapeutic method? systematized bibliographic review / Fraturas metafisárias do rádio distal deslocadas no esqueleto em crescimento: qual é o melhor método terapêutico? revisão bibliográfica sistematizada

Introducción: Las fracturas metafisarias de radio distal son las fracturas más frecuentes en la edad pediátrica, siendo 30% del total de las mismas. Mantener la reducción de las fracturas desplazadas no siempre es posible: el re-desplazamiento es la principal complicación de estas lesiones. Clásicamente se realizó tratamiento con maniobra y yeso, aunque en los últimos años se asoció fijación con Kirschner wire (Kw) en búsqueda de disminuir el re-desplazamiento. El objetivo de nuestro trabajo es identificar factores de riesgo en búsqueda de realizar el mejor tratamiento siendo lo menos agresivo posible. Materiales y métodos: Se realizó una búsqueda sistematizada a través del buscador electrónico PubMed. La misma alcanzó un total de 4594 artículos, que de acuerdo con los criterios de inclusión y exclusión se seleccionaron 15 trabajos para realizar nuestra revisión bibliográfica. Resultados: Se destaca que la mayoría de los artículos encontrados son de nivel de evidencia III y IV. Nuestra búsqueda refleja un índice de re-desplazamiento entre 20-39% mediante yeso a las 2 semanas; asi como un índice de re-manipulación entre el 5-10 % del total de las fracturas desplazadas. La mayoría de los estudios analizados intentan identificar los factores de riesgo más importantes para el re-desplazamiento de las fracturas, de lo que se destacan el grado de desplazamiento inicial de la fractura y la reducción lograda de la misma. A su vez, otros artículos valoran los resultados del tratamiento mediante estabilización con yeso o fijación mediante Kirschner wire. Conclusión: el desplazamiento inicial de la fractura y la reducción lograda en block quirúrgico (BQ) son los factores de riesgo más importantes para el re-desplazamiento. Si bien la técnica de enyesado no es considerado una variable estadísticamente significativa, es considerada una variable importante en cuanto al pronóstico de la lesión, destacando al moldeado de 3 puntos como principal índice a considerar. Se considera aconsejable asociar un Kw en aquellas fracturas cabalgadas en las que no se logra una reducción anatómica en block quirúrgico.

Introduction: Distal radius metaphyseal fractures are the most frequent fractures in pediatric age, accounting for 30% of the total. Maintaining the reduction of displaced fractures is not always possible: re-displacement is the main complication of these injuries. Classically, treatment was performed with a maneuver and a cast, although in recent years fixation with Kirschner wire (Kw) has been associated in search of reducing re-displacement. The objective of our work is to identify risk factors in search of the best treatment while being the least aggressive possible. Materials and methods: A systematic search was carried out using the PubMed electronic search engine. It reached a total of 4594 articles, which according to the inclusion and exclusion criteria, 15 papers were selected for our bibliographic review. Results: It should be noted that most of the articles found are level of evidence III and IV. Our search reflects a re-displacement rate between 20-39% using a cast at 2 weeks; as well as a re-manipulation index between 5-10% of all displaced fractures. Most of the studies analyzed attempt to identify the most important risk factors for the re-displacement of fractures, of which the degree of initial displacement of the fracture and the reduction achieved are highlighted. In turn, other articles assess the results of treatment by stabilization with plaster or fixation with Kirschner wire. Conclusion: the initial displacement of the fracture and the reduction achieved in the surgical block (BQ) are the most important risk factors for re-displacement. Although the casting technique is not considered a statistically significant variable, it is considered an important variable in terms of the prognosis of the injury, highlighting the 3-point casting as the main index to be considered. It is considered advisable to associate a Kw in those mounted fractures in which an anatomical reduction in surgical block is not achieved.

Introdução: As fraturas metafisárias do rádio distal são as mais frequentes na idade pediátrica, correspondendo a 30% do total. Manter a redução das fraturas desviadas nem sempre é possível: o deslocamento é a principal complicação dessas lesões. Classicamente, o tratamento era realizado com manobra e gesso, embora nos últimos anos a fixação com fio de Kirschner (Kw) tenha sido associada na busca pela redução do deslocamento. O objetivo do nosso trabalho é identificar os fatores de risco em busca do melhor tratamento sendo o menos agressivo possível. Materiais e métodos: uma busca sistemática foi realizada usando o mecanismo de busca eletrônico PubMed. Chegou-se a um total de 4.594 artigos, que de acordo com os critérios de inclusão e exclusão, foram selecionados 15 artigos para nossa revisão bibliográfica. Resultados: Ressalta-se que a maioria dos artigos encontrados são de nível de evidência III e IV. Nossa pesquisa reflete uma taxa de re-deslocamento entre 20-39% usando um gesso em 2 semanas; bem como um índice de remanipulação entre 5-10% de todas as fraturas deslocadas. A maioria dos estudos analisados ​​busca identificar os fatores de risco mais importantes para o deslocamento das fraturas, que incluem o grau de deslocamento inicial da fratura e a redução alcançada. Por sua vez, outros artigos avaliam os resultados do tratamento com estabilização gessada ou fixação com fio de Kirschner. Conclusão: o deslocamento inicial da fratura e a redução alcançada no bloqueio cirúrgico (QB) são os fatores de risco mais importantes para o deslocamento. Embora a técnica de gesso não seja considerada uma variável estatisticamente significativa, é considerada uma variável importante em termos de prognóstico da lesão, destacando-se o gesso em 3 pontos como o principal índice a ser considerado. Considera-se aconselhável associar um Kw nas fraturas montadas em que não se consegue redução anatômica no bloqueio cirúrgico.

Long lasting effects of early temperature exposure on the swimming performance and skeleton development of metamorphosing Gilthead seabream (Sparus aurata L.) larvae.

Temperatures experienced during early ontogeny significantly influence fish phenotypes, with clear consequences for the wild and reared stocks. We examined the effect of temperature (17, 20, or 23 °C) during the short embryonic and yolk-sac larval period, on the swimming performance and skeleton of metamorphosing Gilthead seabream larvae. In the following ontogenetic period, all fish were subjected to common temperature (20 °C). The critical swimming speed of metamorphosing larvae was significantly decreased from 9.7 ± 0.6 TL/s (total length per second) at 17 °C developmental temperature (DT) to 8.7 ± 0.6 and 8.8 ± 0.7 TL/s at 20 and 23 °C DT respectively (p < 0.05). Swimming performance was significantly correlated with fish body shape (p < 0.05). Compared with the rest groups, fish of 17 °C DT presented a slender body shape, longer caudal peduncle, terminal mouth and ventrally transposed pectoral fins. Moreover, DT significantly affected the relative depth of heart ventricle (VD/TL, p < 0.05), which was comparatively increased at 17 °C DT. Finally, the incidence of caudal-fin abnormalities significantly decreased (p < 0.05) with the increase of DT. To our knowledge, this is the first evidence for the significant effect of DT during the short embryonic and yolk-sac larval period on the swimming performance of the later stages.

The skeletal maturity of Australian children aged 10-13 years in 2016.

Skeletal maturity can be used as a biological indicator of the tempo of growth in children and adolescents. We present a description of skeletal maturity from a cohort of white Australian children and describe variation in skeletal maturity based on child age. Participants (n = 71; age 10.5-13.9 years) were recruited from the 'Healthy, Active Preschool & Primary Years (HAPPY)' study. Left hand-wrist radiographs were used to determine skeletal maturity using the Tanner-Whitehouse III (TW3) RUS technique. In boys, the mean skeletal maturity offset (bone age - chronological age) was -0.12 ± 0.19 years and 57.9% had delayed skeletal maturity compared to chronological age. Among those with delayed skeletal maturity, the average delay was 0.99 years (range 0.02-2.54 years). In girls, skeletal age was advanced, on average, compared to chronological age by 0.32 ± 0.20 years. Among the 39.4% of girls with delayed skeletal maturity, the average delay was 0.48 years (range: 0.01-2.28). Four children in the sample exhibited a delay in skeletal maturity greater than 2 years. In the context of secular trends towards advanced skeletal maturity observed globally, delayed skeletal maturation in this white, economically privileged cohort are surprising and warrant further exploration.

A comparative genomic database of skeletogenesis genes: from fish to mammals.

Skeletogenesis is a complex process that requires a rigorous control at multiple levels during osteogenesis, such as signaling pathways and transcription factors. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. In present study, we constructed a skeletogenesis database containing 4101, 3715, 2996, 3300, 3719 and 3737 genes in Danio rerio, Oryzias latipes, Gallus gallus, Xenopus tropicalis, Mus musculus and Homo sapiens genome, respectively. Then, we found over 55% of the genes are conserved in the six species. Notably, there are 181 specific-genes in the human genome without orthologues in the other five genomes, such as the ZNF family (ZNF100, ZNF101, ZNF14, CALML6, CCL4L2, ZIM2, HSPA6, etc); and 31 genes are identified explicitly in fish species, which are mainly involved in TGF-beta, Wnt, MAPK, Calcium signaling pathways, such as bmp16, bmpr2a, eif4e1c, wnt2ba, etc. Particularly, there are 20 zebrafish-specific genes (calm3a, si:dkey-25li10, drd1a, drd7, etc) and one medaka-specific gene (c-myc17) that may alter skeletogenesis formation in the corresponding species. The database provides the new systematic genomic insights into skeletal development from teleosts to mammals, which may help to explain some of the complexities of skeletal phenotypes among different vertebrates and provide a reference for the treatment of skeletal diseases as well as for applications in the aquaculture industry.

Morphology of endoskeleton and spination in the sea star Midgardia xandaros (Brisingida: Brisingidae) from the Gulf of Mexico / Morfología del endoesqueleto y ornamentación de la estrella de mar Midgardia xandaros (Brisingida: Brisingidae) en el Golfo de México

Introduction: The deep-sea asteroid species of Brisingida have a nearly global distribution but have remained poorly understood due to their deep bathymetric distributions and fragile skeletons. Objective: To describe the external and internal morphology of Midgardia xandaros including the skeletal arrangement, through multifocal and SEM techniques. Methods: We examined a total of 21 specimens, including 27 arm fragments, from the Gulf of Mexico and Honduras. Two specimens were dissected. Results: Detailed descriptions of pedicellariae, abactinal, intercostal, inferomarginal, adambulacral, ambulacral, odontophore, and oral ossicles, and their spines are provided, emphasizing the articulations and muscle attachments. C-shaped valves pedicellariae and small pedicellariae valves with shorter denticulation areas were recognized. Conclusions: The morphological description of M. xandaros is expanded, providing the most extensive description of abactinal, first adambulacral, first and subsequent inferomarginal ossicles, abactinal spines, and C-shaped, crossed pedicellariae, as well as the distal arm plates, for a brisingid species using SEM to date.

Introducción: Las estrellas de mar de profundidad del orden Brisingida tienen una distribución casi global, sin embargo, han sido poco estudiadas debido a su profunda distribución batimétrica y esqueleto frágil. Objetivo: Describir la morfología externa e interna de Midgardia xandaros incluyendo el arreglo de las placas del esqueleto mediante técnicas de microscopía multifocal y electrónica de barrido (MEB). Métodos: Se examinó un total de 21 ejemplares, incluyendo 27 fragmentos de brazos, provenientes del Golfo de México y Honduras. Dos de estos ejemplares fueron disectados. Resultados: Se presenta la descripción de pedicelarios; placas abactinales, intercostales, inferomarginales, adambulacrales, ambulacrales, orales y odontóforo, y sus espinas, enfatizando los sitios de articulaciones e inserción de músculos. Se reconocieron pedicelarios con valvas con forma de C, y pequeños pedicelarios cuyas valvas poseen áreas de denticulación cortas. Conclusiones: La descripción morfológica de M. xandaros es ampliada, presentado por primera vez la morfología de las placas abactinales, primera adambulacrales, primera y subsecuentes inferomarginales, espinas abactinales y pedicelarios con valvas con forma de "C", así como las placas distales de los brazos para una especie del orden Brisingida.

The gut microbiota is a transmissible determinant of skeletal maturation.

Genetic factors account for the majority of the variance of human bone mass, but the contribution of non-genetic factors remains largely unknown. By utilizing maternal/offspring transmission, cohabitation, or fecal material transplantation (FMT) studies, we investigated the influence of the gut microbiome on skeletal maturation. We show that the gut microbiome is a communicable regulator of bone structure and turnover in mice. In addition, we found that the acquisition of a specific bacterial strain, segmented filamentous bacteria (SFB), a gut microbe that induces intestinal Th17 cell expansion, was sufficient to negatively impact skeletal maturation. These findings have significant translational implications, as the identification of methods or timing of microbiome transfer may lead to the development of bacteriotherapeutic interventions to optimize skeletal maturation in humans. Moreover, the transfer of SFB-like microbes capable of triggering the expansion of human Th17 cells during therapeutic FMT procedures could lead to significant bone loss in fecal material recipients.

Comparison of cervical vertebral anomalies and sella turcica bridging in different growth stages with various vertical skeletal growth patterns.

PURPOSE: To compare cervical vertebral anomalies and sella turcica bridging (STB) in different growth stages in orthodontic patients with different vertical skeletal growth patterns. METHODS: Lateral cephalometric radiographs (LCR) of 270 patients in the preadolescent, adolescent, or postadolescent periods and having low angle [LA], normal angle [NA], or high-angle [HA] vertical skeletal growth patterns were evaluated retrospectively. STB was visualized using LCRs while evaluating the deficiency of ponticulus posticus (PP) and atlas posterior arch (PAA) associated with the atlas bone. The Pearson chi-square and Fisher's exact tests were used for categorical data and one-way ANOVA for numerical data. RESULTS: The prevalence of fully calcified PP and STB increased from the preadolescent (PP, 10.0%; STB, 11.1%) to the postadolescent period (PP, 24.4; STB, 21.1%); they did not differ from vertical skeletal growth patterns (p > 0.05). The prevalence of PAA deficiency is significantly higher in individuals with LA (46.7%) than with other angles (NA, 27.8%; HA, 26.7%). The vertical skeletal growth pattern was significantly related to STB in the preadolescent period and PAA in the postadolescent period. CONCLUSIONS: Different anomalies during different growth periods correlate with the vertical skeletal growth pattern. It will be useful to evaluate a different anomaly according to the relevant growth period.

Postnatal ossification sequences in Acrocephalus scirpaceus and Chroicocephalus ridibundus (Aves: Neognathae): The precocial-altricial spectrum and evolution of compound bones in birds.

Although the development of the avian skeleton has attracted considerable attention, most of the studies have been concentrated on the embryonic period, while studies on the postnatal period are rare. We studied the postnatal development of the skeleton in two phylogenetically distant birds, an altricial passerine Acrocephalus scirpaceus and a semiprecocial charadriiform Chroicocephalus ridibundus. The neonates of the former, despite being altricial, have well-ossified skeleton-the degree of development approaches that of the semiprecocial gull. However, after hatching the limb bones (particularly those of the hind limb) ossify earlier in the gull which is probably related to faster acquisition of locomotor abilities. We have observed that, in contrast to previous reports from neognathous birds, in the ankle of the gull, the ascending process fuses with the astragalus rather than with the calcaneum. This type of development is present in palaeognaths and nonavian dinosaurs but has not yet been reported in neognaths. This indicates a greater diversity within Neognathae and suggests a more complex scenario for the evolution of the avian ankle. However, data from a greater number of species are needed to establish the developmental sequence ancestral for neognathous birds. Furthermore, the sequence of bone fusions in the wrist of Acrocephalus is similar to the fossil-documented evolutionary sequence observed in the phylogeny of early birds, with the semilunate carpal and major metacarpal fusing first, followed by the alular metacarpal fusing with the major metacarpal and then the major and minor metacarpal fusing proximally. These data underscore the importance of developmental studies for reconstructing the evolutionary history.

Endochondral growth zone pattern and activity in the zebrafish pharyngeal skeleton.

BACKGROUND: Endochondral ossification is a major bone forming mechanism in vertebrates, defects in which can result in skeletal dysplasia or craniofacial anomalies in humans. The zebrafish holds great potential to advance our understanding of endochondral growth zone development and genetics, yet several important aspects of its biology remain unexplored. Here we provide a comprehensive description of endochondral growth zones in the pharyngeal skeleton, including their developmental progression, cellular activity, and adult fates. RESULTS: Postembryonic growth of the pharyngeal skeleton is supported by endochondral growth zones located either at skeletal epiphyses or synchondroses. Col2a1a and col10a1a in situ hybridization and anti-PCNA immunostaining identify resting-, hypertrophic- and proliferative zones, respectively, in pharyngeal synchondroses. Cellular hypertrophy and matrix deposition contribute little, if at all, to axial growth in most skeletal elements. Zebrafish endochondral growth zones develop during metamorphosis and arrest in adults. CONCLUSIONS: Two endochondral growth zone configurations in the zebrafish pharyngeal skeleton produce either unidirectional (epiphyses) or bidirectional (synchondroses) growth. Cell proliferation drives endochondral growth and its modulation, in contrast to mammalian long bones in which bone length depends more on cell enlargement during hypertrophy and intramembranous ossification is the default mechanism of bone growth in zebrafish adults.

Impact of various ecological parameters on the life-history characteristics of Bufotes viridis sitibundus from Turkey.

In this study, we used the skeletochronology method to estimate various growth parameters, such as age structure, minimum and maximum life span, age of sexual maturity, and the relationship between body size and weight of eight different populations of the variable toad, Bufotes viridis sitibundus, in Turkey. Further, we determined the relationship between these parameters and ecologic factors using the partial Mantel test. A significant difference was found among the populations with respect to age, body size, and body weight in both males and females. On average, the maximum life span was recorded as 10 years for males and 11 years for females. In the studied populations, the average age of sexual maturity ranged between 2 and 4 years for both sexes. Sexual dimorphism in terms of snout-vent length (SVL) was not observed between males and females in all the populations. Toads from the higher altitudes tended to be significantly larger, older, and heavier than those from lower altitudes. We concluded that altitude and temperature have an impact on the growth rate, body size, and body mass.

CANT1 deficiency in a mouse model of Desbuquois dysplasia impairs glycosaminoglycan synthesis and chondrocyte differentiation in growth plate cartilage.

Desbuquois dysplasia (DD) type 1 is a rare skeletal dysplasia characterized by a short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium-activated nucleotidase 1 (CANT1), which encodes a nucleotidase that preferentially hydrolyzes UDP to UMP and phosphate. In this study, we generated Cant1 KO mice using CRISPR/Cas9-mediated genome editing. All F0 mice possessing frameshift deletions at both Cant1 alleles exhibited a dwarf phenotype. Germline transmission of the edited allele was confirmed in an F0 heterozygous mouse, and KO mice were generated by crossing of the heterozygous breeding pairs. Cant1 KO mice exhibited skeletal defects, including short stature, thoracic kyphosis, and delta phalanx, all of which are observed in DD type 1 patients. The glycosaminoglycan (GAG) content and extracellular matrix space were reduced in the growth plate cartilage of mutants, and proliferating chondrocytes lost their typical flat shape and became round. Chondrocyte differentiation, especially terminal differentiation to hypertrophic chondrocytes, was impaired in Cant1 KO mice. These findings indicate that CANT1 is involved in the synthesis of GAG and regulation of chondrocyte differentiation in the cartilage and contribute to a better understanding of the pathogenesis of DD type 1.

Impact of feeding microalgae (Aurantiochytrium limacinum) and co-extruded mixture of full-fat flaxseed as sources of n-3 fatty acids to ISA brown and Shaver white breeders and progeny on pullet skeletal attributes at hatch through to 18 weeks of age.

Impact of feeding n-3 fatty acids (FA) to ISA brown and Shaver white breeders and their progeny on bone development in pullets was investigated. Breeders were fed Control (CON); CON + 1% microalgae (DMA: Aurantiochytrium limacinum) as the source of docosahexaenoic acid; and CON + 2.6% of a co-extruded mixture of full-fat flaxseed (FFF) and pulses mixture as source of α-linolenic acid. Test diets (DMA and FFF) were balanced for total n-3 FA and n-6: n-3 FA ratio. Samples of day-old progeny were euthanized for bone mineral content (BMC) and tibia collagen type II. The remaining pullets were fed posthatch treatments as follows: from breeder CON: CON (CON-CON), DMA (CON-DMA), and FFF (CON-FFF), from breeder DMA: CON (DMA-CON) and DMA (DMA-DMA) and from breeder FFF: CON (FFF-CON) and FFF (FFF-FFF). A total of 60 pullets per posthatch diets were reared in cages (12 pullets/cage, n = 5) with free access to feed and water, bled at 6, 12, and 18 wk of age (WOA) for bone turnover markers and necropsied at 18 WOA for tibia and femur samples. Day-old pullets from breeder fed CON had greater BMC (P < 0.001) relative to those from breeders fed other diets. There was strain and diet interaction (P ≤ 0.024) on tibia breaking strength (TBS) and tibia cortical ash concentration at 18 WOA such that diet responses were only observed in Shaver white pullets. In this context, TBS of DMA-DMA and FFF-FFF was greater than for pullets originating from CON breeder, and the cortical ash weight of DMA-DMA and FFF-FFF pullets was 23.8 and 20.2%, respectively, higher than for CON-CON pullets. In conclusions, the strain effects were strong on tibia attributes on 18-week-old pullets. Breeder feeding of n-3 FA was more effective when concomitant with posthatch feeding of n-3 FA in supporting the skeletal strength and cortical bone development in Shaver white pullets. Further investigations are warranted to establish the impact these strategies on skeletal health during laying cycle.

Effects of phthalate acid esters on zebrafish larvae: Development and skeletal morphogenesis.

This study evaluated the acute developmental toxicity of six priority phthalic acid esters (PAEs) including dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DNOP), and benzyl butyl phthalate (BBP) in zebrafish embryos. A novel alcian blue and alizarin red double staining was performed to detect skeletal development of zebrafish larvae. Results revealed that all six PAEs could induce different developmental abnormalities in zebrafish larvae, including abnormal movement, decreased heart rate, spinal curvature, and pericardial edema. The bone development of zebrafish larvae exposed to PAEs was also affected by PAEs acute exposure. Among PAEs, DBP, and BBP even at low doses can cause mortality in zebrafish, implying their higher toxicity. Contrarily, DEHP and DNOP showed minor effects on the developmental morphology of zebrafish larvae. However, the gene expression levels of skeleton-related genes showed the upregulation of the runx2b and shha genes after DEHP and DBP exposure. Taken together, the strict use and release of PAEs in the environment should be supervised by the government for ecological and environmental safety.

Lipid phosphatase SHIP-1 regulates chondrocyte hypertrophy and skeletal development.

SH2-containing inositol-5'-phosphatase-1 (SHIP-1) controls the phosphatidylinositol-3'-kinase (PI3K) initiated signaling pathway by limiting cell membrane recruitment and activation of Akt. Despite the fact that many of the growth factors important to cartilage development and functions are able to activate the PI3K signal transduction pathway, little is known about the role of PI3K signaling in chondrocyte biology and its contribution to mammalian skeletogenesis. Here, we report that the lipid phosphatase SHIP-1 regulates chondrocyte hypertrophy and skeletal development through its expression in osteochondroprogenitor cells. Global SHIP-1 knockout led to accelerated chondrocyte hypertrophy and premature formation of the secondary ossification center in the bones of postnatal mice. Drastically higher vascularization and greater number of c-kit + progenitors associated with sinusoids in the bone marrow also indicated more advanced chondrocyte hypertrophic differentiation in SHIP-1 knockout mice than in wild-type mice. In corroboration with the in vivo phenotype, SHIP-1 deficient PDGFRα + Sca-1 + osteochondroprogenitor cells exhibited rapid differentiation into hypertrophic chondrocytes under chondrogenic culture conditions in vitro. Furthermore, SHIP-1 deficiency inhibited hypoxia-induced cellular activation of Akt and extracellular-signal-regulated kinase (Erk) and suppressed hypoxia-induced cell proliferation. These results suggest that SHIP-1 is required for hypoxia-induced growth signaling under physiological hypoxia in the bone marrow. In conclusion, the lipid phosphatase SHIP-1 regulates skeletal development by modulating chondrogenesis and the hypoxia response of the osteochondroprogenitors during endochondral bone formation.