Search

Background: Changes in bone age and tooth development are late side effects of cancer therapy and can be identified by imaging examination. Aim: To evaluate the late effects of antineoplastic treatment on bone age and dental development in childhood cancer survivors. Design: This is a retrospective case–control study on paediatric cancer survivors of both sexes who underwent antineoplastic treatment with 5–15 years of survival. Carpal radiographs were assessed for bone age and growth curve, and panoramic radiographs were used to evaluate dental development and alterations. Carpal radiographs were analyzed using the Greulich and Pyle inspection method, and the Martins and Sakima method was used to analyze the growth curve. All tests were applied with a confidence level of 95%. Results: The study and control groups comprised 28 and 56 patients, respectively. There was no significant difference in bone age and growth curve between the study and control groups. Nonetheless, when sex was compared to chronological and bone ages, there was a significant difference in bone age (p = 0.019) and an underestimation in both groups and sexes in the Greulich and Pyle method. As to late dental effects, dental agenesia, microdontia, gyroversion, and unerupted teeth were found. Dental shape alterations mainly involve the root region. Conclusion: Close multidisciplinary collaboration is necessary during the follow‐up period of young patients who have survived cancer. [ABSTRACT FROM AUTHOR]

The study evaluated the effects of nutritional strategies on broilers challenged with Eimeria from d 14 to 26. A total of 840 Cobb male broilers were fed five diets in a 2 × 5 factorial arrangement: 1) nutrient adequate diet (PC; 0.84% calcium [Ca], 0.42% available phosphorus [avP]); 2) Ca-P deficient diet (NC; 0.64% Ca, 0.22% avP); 3) NC + 1500 FTU/kg phytase of diet (NC + PHY); 4) NC + 5000 IU/kg 25-hydroxycholecalciferol of diet (NC + 25OHD); and 5) NC with both supplements (NC + PHY + 25OHD), with and without Eimeria challenge. All treatments had six replicate cages with 14 birds per cage. At 5 days post inoculation (DPI), the challenged birds exhibited higher serum fluorescein isothiocyanate-d (FITC-d) levels than the unchallenged birds (P

Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers and show that they provide a mechanistic framework through which non-coding genetic variants can influence skeletal development and human stature. Working with fetal chondrocytes isolated from mice bearing a Col2a1 fluorescent regulatory sensor, we identify 780 genes and 2'704 putative enhancers specifically active in chondrocytes using a combination of RNA-seq, ATAC-seq and H3K27ac ChIP-seq. Most of these enhancers (74%) show pan-chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. Notably, genetic variations overlapping these enhancers better explain height differences than those overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3, Col2a1, Hhip and, Nkx3-2 loci confirm their role in regulating cognate genes. This enhancer map provides a framework for understanding how genes and non-coding variations influence bone development and diseases.

ZC4H2 encodes a C4H2-type zinc finger protein, mutations of which lead to a spectrum of diseases known as ZC4H2 associated rare disorders (ZARD). In addition to neurological phenotypes, the most typical symptoms of ZARD are multiple joint contractures of varying degrees, accompanied by abnormal development of muscles and bones, and osteoporosis in some cases. The pathogenic mechanisms of such bone related phenotypes, however, remain unclear. Here, we showed that ZC4H2 is expressed in the developing bones in mice. ZC4H2 knockout mice were neonatal-lethal and smaller in size, with reduced calcification of long bones. Upon induced loss of ZC4H2 postnatally, the femoral bones developed an osteoporosis-like phenotype, with reduced bone mineral density, bone-volume fraction, and trabecular bone number. Knockdown of ZC4H2 showed no clear effect on the expression of osteogenic differentiation genes in in vitro models using mesenchymal stem cells. Interestingly, ZC4H2 knockdown significantly enhanced osteoclast differentiation and bone resorption in induced bone marrow-derived macrophages. We further confirmed that the number of osteoclasts in the long bone of ZC4H2 knockout mice was increased, as well as the expression of the serum bone resorption/osteoporosis marker CTX-1. Our study unveils a new role of ZC4H2 in osteoclast differentiation and bone development, providing new clues on the pathology of ZARD. [ABSTRACT FROM AUTHOR]

The skeleton plays a fundamental role in the maintenance of organ function and daily activities. The insulin‐like growth factor (IGF) family is a group of polypeptide substances with a pronounced role in osteoblast differentiation, bone development, and metabolism. Disturbance of the IGFs and the IGF signaling pathway is inextricably linked with assorted developmental defects, growth irregularities, and jeopardized skeletal structure. Recent findings have illustrated the significance of the action of the IGF signaling pathway via growth factors and receptors and its interactions with dissimilar signaling pathways (Wnt/β‐catenin, BMP, TGF‐β, and Hh/PTH signaling pathways) in promoting the growth, survival, and differentiation of osteoblasts. IGF signaling also exhibits profound influences on cartilage and bone development and skeletal homeostasis via versatile cell–cell interactions in an autocrine, paracrine, and endocrine manner systemically and locally. Our review summarizes the role and regulatory function as well as a potentially integrated gene network of the IGF signaling pathway with other signaling pathways in bone and cartilage development and skeletal homeostasis, which in turn provides an enlightening insight into visualizing bright molecular targets to be eligible for designing effective drugs to handle bone diseases and maladies, such as osteoporosis, osteoarthritis, and dwarfism. [ABSTRACT FROM AUTHOR]

Tissue-resident stem cells are essential for development and repair, and in the skeleton, this function is fulfilled by recently identified skeletal stem cells (SSCs). However, recent work has identified that SSCs are not monolithic, with long bones, craniofacial sites, and the spine being formed by distinct stem cells. Recent studies have utilized techniques such as fluorescence-activated cell sorting, lineage tracing, and single-cell sequencing to investigate the involvement of SSCs in bone development, homeostasis, and disease. These investigations have allowed researchers to map the lineage commitment trajectory of SSCs in different parts of the body and at different time points. Furthermore, recent studies have shed light on the characteristics of SSCs in both physiological and pathological conditions. This review focuses on discussing the spatiotemporal distribution of SSCs and enhancing our understanding of the diversity and plasticity of SSCs by summarizing recent discoveries. [ABSTRACT FROM AUTHOR]

Preclinical models (typically ovariectomized rats and genetically altered mice) have underpinned much of what we know about skeletal biology. They have been pivotal for developing therapies for osteoporosis and monogenic skeletal conditions, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and craniodysplasias. Further therapeutic advances, particularly to improve cortical strength, require improved understanding and more rigorous use and reporting. We describe here how trabecular and cortical bone structure develop, are maintained, and degenerate with aging in mice, rats, and humans, and how cortical bone structure is changed in some preclinical models of endocrine conditions (eg, postmenopausal osteoporosis, chronic kidney disease, hyperparathyroidism, diabetes). We provide examples of preclinical models used to identify and test current therapies for osteoporosis, and discuss common concerns raised when comparing rodent preclinical models to the human skeleton. We focus especially on cortical bone, because it differs between small and larger mammals in its organizational structure. We discuss mechanisms common to mouse and human controlling cortical bone strength and structure, including recent examples revealing genetic contributors to cortical porosity and osteocyte network configurations during growth, maturity, and aging. We conclude with guidelines for clear reporting on mouse models with a goal for better consistency in the use and interpretation of these models. [ABSTRACT FROM AUTHOR]

Abstract Males and females have long shown disparities in body weight and height; yet, the underlying mechanisms influencing growth and development remain unclear. Male and female Zhedong White Geese (ZDW) geese have long been selected for large body size and egg production, respectively. This led to a large difference in body weight between males and females, making them a unique model for studying the effects of sex on growth and development. This study aimed to elucidate these mechanisms by comparing the transcriptomes of muscle and pituitary tissues in male and female ZDW geese to identify the critical genes responsible for the effects of sex on growth performance. Our analysis revealed 1101 differentially expressed genes (DEGs) in leg musculature (507 upregulated, 594 downregulated), 773 DEGs in breast musculature (311 upregulated, 462 downregulated), and 517 DEGs in the pituitary gland (281 upregulated, 236 downregulated) between male and female geese. These DEGs were significantly enriched in gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with endocrine metabolism (e.g., hormonal activities), muscle formation (e.g., sarcomere and myofibril), and bone formation (e.g., bone morphogenesis and cartilage formation). The upregulated genes in males were enriched in KEGG pathways involving nutrient digestion and absorption (vitamin and protein), as well as the secretion of digestive juices (gastric acid and bile). Through protein–protein interaction analyses, we also observed high-density gene networks related to muscle fiber development, calcium ion metabolism, mitochondrial respiratory chain, and bone development. Therefore, our multi-tissue transcriptome analysis provides a deeper understanding of the complex and systematic gender-driven effects on growth and development in geese. IGF1, GHRHR, and NCAPG-LCORL and pathways related to myogenesis might play vital roles in gender differences before hormones exert their effect.

Abstract The aim of the present study was to examine the growth dynamics of the two ossification centers of the body of sphenoid bone in the human fetus, based on their linear, planar and volumetric parameters. The examinations were carried out on 37 human fetuses of both sexes aged 18–30 weeks of gestation, which had been preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, we evaluated the size of the presphenoid and postsphenoid ossification centers. The presphenoid ossification center grew proportionately in sagittal diameter, projection surface area and volume, and logarithmically in transverse diameter. The postsphenoid ossification center increased logarithmically in sagittal diameter, transverse diameter and projection surface area, while its volumetric growth followed proportionately. The numerical findings of the presphenoid and postsphenoid ossification centers may be considered age-specific reference values of potential relevance in monitoring the normal fetal growth and screening for congenital disorders in the fetus. The obtained results may contribute to a better understanding of the growing fetal skeleton, bringing new numerical information regarding its diagnosis and development.

Throughout pregnancy, maternal thyroid-related hormones are transported to the fetus via the placenta to allow normal fetal growth and development and are particularly important in the first and second trimesters of pregnancy. During maternal-fetal transport, in addition to thyroid-related hormones, thyroid-stimulating hormone receptor antibodies and antithyroid drugs can enter the fetus and interfere with development of the fetal thyroid gland and endocrine function, potentially leading to hyperthyroidism or hypothyroidism in the fetus or newborn. Several basic studies have been performed to demonstrate the important role of thyroid-related hormones in fetal and neonatal bone development. Ultrasound can assess neonatal skeletal maturity and bone development safely, rapidly, and effectively. This review aims to communicate the latest knowledge about maternal and fetal thyroid function in both normal and pathological pregnancies and summarize the latest advances in the potential effects of abnormal maternal thyroid function on bone development in the fetus and neonate. Finally, it discusses recent advances in research on ultrasound in the assessment of fetal and neonatal bone development.

Males and females have long shown disparities in body weight and height; yet, the underlying mechanisms influencing growth and development remain unclear. Male and female Zhedong White Geese (ZDW) geese have long been selected for large body size and egg production, respectively. This led to a large difference in body weight between males and females, making them a unique model for studying the effects of sex on growth and development. This study aimed to elucidate these mechanisms by comparing the transcriptomes of muscle and pituitary tissues in male and female ZDW geese to identify the critical genes responsible for the effects of sex on growth performance. Our analysis revealed 1101 differentially expressed genes (DEGs) in leg musculature (507 upregulated, 594 downregulated), 773 DEGs in breast musculature (311 upregulated, 462 downregulated), and 517 DEGs in the pituitary gland (281 upregulated, 236 downregulated) between male and female geese. These DEGs were significantly enriched in gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with endocrine metabolism (e.g., hormonal activities), muscle formation (e.g., sarcomere and myofibril), and bone formation (e.g., bone morphogenesis and cartilage formation). The upregulated genes in males were enriched in KEGG pathways involving nutrient digestion and absorption (vitamin and protein), as well as the secretion of digestive juices (gastric acid and bile). Through protein–protein interaction analyses, we also observed high-density gene networks related to muscle fiber development, calcium ion metabolism, mitochondrial respiratory chain, and bone development. Therefore, our multi-tissue transcriptome analysis provides a deeper understanding of the complex and systematic gender-driven effects on growth and development in geese. IGF1, GHRHR, and NCAPG-LCORL and pathways related to myogenesis might play vital roles in gender differences before hormones exert their effect. [ABSTRACT FROM AUTHOR]

[Display omitted] Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3 lysine 27 acetylation (H3K27ac) at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders. [ABSTRACT FROM AUTHOR]

Epigenetic modifications affect cell differentiation via transcriptional regulation. G9a/EHMT2 is an important epigenetic modifier that catalyzes the methylation of histone 3 lysine 9 (H3K9) and interacts with various nuclear proteins. In this study, we investigated the role of G9a in osteoclast differentiation. When we deleted G9a by infection of Cre‐expressing adenovirus into bone marrow macrophages (BMMs) from G9afl/fl(Ehmt2fl/fl) and induced osteoclastic differentiation by the addition of macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL), the number of TRAP‐positive multinucleated osteoclasts significantly increased compared with control. Furthermore, the mRNA expression of osteoclast markers, TRAP, and cathepsin K, and to a lesser extent, NFATc1, a critical transcription factor, increased in G9a KO cells. Infection of wild‐type (WT) G9a‐expressing adenovirus in G9a KO cells restored the number of TRAP‐positive multinucleated cells. In G9a KO cells, increased nuclear accumulation of NFATc1 protein and decreased H3K9me2 accumulation were observed. Furthermore, ChIP experiments revealed that NFATc1 binding to its target, Ctsk promoter, was enhanced by G9a deletion. For in vivo experiments, we created G9a conditional knock‐out (cKO) mice by crossing G9afl/fl mice with RankCre/+ (Tnfrsf11aCre/+) mice, in which G9a is deleted in osteoclast lineage cells. The trabecular bone volume was significantly reduced in female G9a cKO mice. The serum concentration of the C‐terminal telopeptide of type I collagen (CTX), a bone‐resorbing indicator, was higher in G9a cKO mice. In addition, osteoclasts differentiated from G9a cKO BMMs exhibited greater bone‐resorbing activity. Our findings suggest that G9a plays a repressive role in osteoclastogenesis by modulating NFATc1 function. [ABSTRACT FROM AUTHOR]

Physiological processes within the human body are regulated in approximately 24‐h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders. [ABSTRACT FROM AUTHOR]

Copyright of Die Gynäkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bone is a metabolically dynamic structure that is generally remodeled throughout the lifetime of an individual but often causes problems with increasing age. A key player for bone development and homeostasis, but also under pathological conditions, is the bone vasculature. This complex system of arteries, veins, and capillaries forms distinct structures where each subset of endothelial cells has important functions. Starting with the basic process of angiogenesis and bone-specific blood vessel formation, coupled with initial bone formation, the importance of different vascular structures is highlighted with respect to how these structures are maintained or changed during homeostasis, aging, and pathological conditions. After exemplifying the current knowledge on bone vasculature, this review will move on to exosomes, a novel hotspot of scientific research. Exosomes will be introduced starting from their discovery via current isolation procedures and state-of-the-art characterization to their role in bone vascular development, homeostasis, and bone regeneration and repair while summarizing the underlying signal transduction pathways. With respect to their role in these processes, especially mesenchymal stem cell-derived extracellular vesicles are of interest, which leads to a discussion on patented applications and an update on ongoing clinical trials. Taken together, this review provides an overview of bone vasculature and bone regeneration, with a major focus on how exosomes influence this intricate system, as they might be useful for therapeutic purposes in the near future. [ABSTRACT FROM AUTHOR]

The worldwide trend toward an aging population has resulted in a higher incidence of chronic conditions, such as osteoporosis. Osteoporosis, a prevalent skeletal disorder characterized by decreased bone mass and increased fracture risk, encompasses primary and secondary forms, each with distinct etiologies. Mechanistically, osteoporosis involves an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Current pharmacological interventions for osteoporosis, such as bisphosphonates, denosumab, and teriparatide, aim to modulate bone turnover and preserve bone density. Hormone replacement therapy and lifestyle modifications are also recommended to manage the condition. While current medications offer therapeutic options, they are not devoid of limitations. Recent studies have highlighted the importance of epigenetic mechanisms, including DNA methylation and histone modifications, in regulating gene expression during bone remodeling. The use of epigenetic drugs, or epidrugs, to target these mechanisms offers a promising avenue for therapeutic intervention in osteoporosis. In this review, we comprehensively examine the recent advancements in the application of epidrugs for treating osteoporosis. [ABSTRACT FROM AUTHOR]

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment‐to‐lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH. [ABSTRACT FROM AUTHOR]

Copyright of Revista ADM is the property of Asociacion Dental Mexicana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundDespite the critical role of the clavicle in understanding growth and development in early childhood, there remains a notable paucity of comprehensive studies investigating clavicle growth patterns during this crucial period. This hinders our ability to establish normative growth parameters during these early life stages. Our study sought to measure clavicle dimensions and subsequently construct growth curves spanning from preterm infants to toddlers up to the age of 6 years by measuring routine chest radiographs. Differences between both sides of the body and between the sexes should be analysed. This aimed to provide a nuanced understanding of clavicle growth dynamics and offering a foundation for the establishment of normative values in this understudied context. In this retrospective study, children aged 23 weeks of gestation to 6 years who underwent a chest radiography between January 2010 and June 2020 were enrolled. A total of 5.311 potential radiographs was screened. Clavicle length and width were measured in all radiographs using the Centricity™ Universal Viewer. Statistical analysis was performed using SPSS®.Results1.340 images met the quality criteria to be included in our study. The growth curves of clavicle lengths and widths showed a steadily increasing trend with age. Inclusion of premature infants in the age group of one month resulted in a decrease in this age group. Significant differences between both sides of the body and between the sexes could be shown. Measurements of clavicle length and width, derived from routine chest radiographs, are highly accurate. This accuracy underscores the potential for utilizing thoracic radiographs as a reliable tool for assessing clavicle growth in clinical settings or even forensic analysts. The establishment of reference values derived from our measurements provides a basis for normative growth parameters.

ABSTRACT: Leg disorders have become increasingly common in broilers, leading to lower meat quality and major economic losses. This study evaluated the effects of dietary supplementation with Clostridium butyricum (C. butyricum) and 25-hydroxyvitamin D3 (25-OH-D3) on bone development by comparing growth performance, tibial parameters, Ca and P contents of tibial ash, bone development-related indicators’ level, and cecal short-chain fatty acids in Cobb broilers. All birds were divided into four treatment groups, which birds fed either a basal diet (Con), basal diet + 75 mg chlortetracycline/kg (Anti), basal diet + C. butyricum at 109 CFU/kg (Cb), basal diet + C. butyricum at 109 CFU/kg and 25-OH-D3 at 25 μg/kg (CbD), or basal diet + 25-OH-D3 at 25 μg/kg (CD). Our results suggest that the dietary supplementation in Cb, CbD, and CD significantly increased the body weight (BW) and average daily gain (ADG), and reduced the feed-to-weight ratio (F/G) at different stages of growth (P < 0.05). Dietary supplementation in Cb, CbD, and CD prolonged (P < 0.05) the behavioral responses latency-to-lie (LTL) time, reduced (P < 0.05) the levels of osteocalcin (BGP) and peptide tyrosine (PYY), and increased (P < 0.05) serotonin (5-HT) and dopamine (DA). Treatment with Cb increased (P < 0.05) the levels of acetic acid, isobutyric acid, butyric acid, and isovaleric acid compared with those in Con group. The cecal metagenome showed that Alistipes spp. were significantly more abundant in Cb, CbD, and CD groups (P < 0.05). A total of 12 metabolic pathways were significantly affected by supplementation, including the signaling pathways of glucagon, insulin, and PI3K-AKT; primary and secondary bile acid biosynthesis; and P-type Ca 2+ transporters (P < 0.05). Hence, the CbD supplementation modulates bone metabolism by regulating the mediators of gut–brain axis, which may inform strategies to prevent leg diseases and improve meat quality in broilers.

ObjectivesTo study total growth, rate of bone maturation, and menarche after discontinuation of Gonadotropin releasing hormone agonist (GnRHa) treatment for central precocious puberty (CPP).MethodsTwenty girls with CPP on treatment with GnRHa were followed from discontinuation of treatment to final height (FH). Height, height velocity (HV), and bone age were measured every 6 months. Age at menarche was collected.ResultsOnce treatment is discontinued, rate of bone maturation (bone age [BA]/chronological [CA]) accelerated from 0.7 ± 0.3 at end of treatment to 1.2 ± 0.8 post treatment, similar to BA/CA prior to treatment. BA at treatment discontinuation ranged from 11-14 years. On average, treatment was stopped when CA was within 9 months of BA. All girls continued to grow from end of treatment to menarche averaging an increase of 4.7 ± 3.7 cm, with HV 3.2 ± 2.0 cm/year. Post-menarche they grew an additional 4.6 ± 2.1 cm, with HV 2.4 ± 1.9 cm/year. Acceleration of HV was not seen post treatment. The younger the BA at initiation or completion of treatment, the longer time to menarche. No one had menarche prior to a BA of 12.5 year.ConclusionsA pubertal growth spurt does not usually occur after treatment with GnRHa in girls with CPP. Rate of bone maturation accelerates post treatment. These factors are important in assessing optimal height outcome and decisions regarding cessation of treatment. This study will help clinicians give patients and families better estimates of growth and onset of menarche post treatment.

Skull growth involves the expansion of both the flat calvarial bones of the skull and the fibrous marginal zones, termed sutures, between them. This process depends on co‐ordinated proliferation of mesenchymal‐derived progenitor cells within the sutures, and their differentiation to osteoblasts which produce the bone matrix required to expand the size of the bony plates. Defects lead to premature closure of these sutures, termed craniosynostosis, resulting in heterogeneous head shape differences due to restricted growth of one or more sutures. The impact on the individual depends on how many and which sutures are affected and the severity of the effect. Several genetic loci are responsible, including a wide range of variants in the gene for the interleukin 11 receptor (IL11RA, OMIM#600939). Recent work from Kespohl and colleagues provides new insights into how some of these variants influence IL‐11R function; we discuss their influences on IL‐11R structure and IL‐11 function as a stimulus of osteoblast differentiation. [ABSTRACT FROM AUTHOR]

Several studies have documented the occurrence of hyperostosis, a bone condition that results in bone thickening, in specimens of Trichiurus lepturus, an important commercial species. A total of 102 Largehead Hairtail fish samples from Rio de Janeiro, Brazil, were obtained from artisanal fishers and divided into 4 size classes. Biometric measurements and radiographic images were taken for all exemplars. Hyperostosis was observed in 69.69% of the individuals, with the first detection of the condition in an exemplar measuring from 385 mm in total length. The affected skeletal regions included the cleithrum, supraoccipital, frontal, dorsal pterygiophores, and haemal spines. An increase in the occurrence frequency of hyperostosis was noticed in correlation with size, suggesting a connection with the aging process and an ontogenetic pattern for the species. Histological analysis indicated a high remodeling process in affected structures. In addition, we highlight the specie daily vertical migration, associated with temperature variation, as a potential contributor to the onset of this osteological condition in marine teleosts. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effect of pomegranate juice consumption on bone histomorphometric parameters using an animal model. The animals (rats) were divided into 7 experimental groups. The groups differed in the concentration of pomegranate juice administered. The control group received only water, the other groups were supplied with commercial or freshly squeezed pomegranate juice at concentrations of 10%, 25% and 50%. To study the structure of the proximal end of the tibia, a Skyscan 1174 X-ray microtomography device, equipped with a 1.3Mp FW VDS camera, was used. The proximal end (metaphysis) of the left tibia was examined. The following bone tissue parameters were analysed: bone mineral density (BMD) (mm3), the number of trabeculae (Tb.N) (mm-1), trabecular separation (Tb.Sp) (mm) and trabecular thickness (Tb. Th) (mm), BS/BV(mm-1). It was found that 25% pomegranate juice, both freshly squeezed and commercial, significantly increased bone density (BMD), increased trabecular thickness (Tb.TH), and reduced the distance between trabeculae (Tb.SP) compared to the control group and groups receiving juice at other concentrations. The highest BMD, the thickest trabeculae and the smallest distance between trabeculae were observed after the application of fresh 25% pomegranate juice. Thus, it can be concluded that pomegranate juice, especially freshly squeezed, improves bone density. [ABSTRACT FROM AUTHOR]

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non‐endosteal perisinusoidal niche. Single‐cell molecular profiling and in vivo cell lineage analyses play key roles in discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor‐making cells when deleterious mutations occur in tumor suppressor genes. The emerging hypothesis is that osteoblast‐chondrocyte transitional identities confer a special subset of endosteal stromal cells with stem cell‐like properties, which may make them susceptible for tumorigenic transformation. Endosteal stem cells are likely to represent an important therapeutic target of bone diseases caused by aberrant bone formation. [ABSTRACT FROM AUTHOR]

Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis. [ABSTRACT FROM AUTHOR]

Marine teleost species of commercial interest are often reported with hyperostosis, an osteological condition that results in bone thickening. Various specimens of Atlantic Spadefish Chaetodipterus faber (n = 86) obtained from artisanal fishermen in Rio de Janeiro, Brazil, were radiographed and assessed to detect the occurrence of hyperostosis across four different size classes. Of the examined individuals, 58.62% displayed signs of hyperostosis, which manifested in eight skeletal regions, notably in the supraoccipital crest, cleithrum and supraneural areas. In the vertebral column, hyperostosis was more frequently observed in haemal spines than in neural spines, predominantly between the sixth and eighth caudal vertebrae. The smallest size class (<200 mm total length) showed a low frequency of hyperostosis at 7.89%. This frequency escalated for larger classes, reaching 94.12% in individuals measuring 200–300 mm in total length and was observed in all individuals exceeding 300 mm. Hyperostosis exhibited an ontogenetic development pattern, where both the occurrence frequencies and the sizes of the affected bones expanded in proportion to the fish size. This is the first description of the hyperostosis pattern of development for the species, an important commercial resource. [ABSTRACT FROM AUTHOR]

Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human NINEIN gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts, whereas the number of osteoblasts remains unaffected. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.

ABSTRACT Purpose: To evaluate the inductive capacity of F18 bioglass putty on the induced membrane technique in a segmental bone defect of the rabbit’s radius. Methods: Ten female Norfolk at 24 months of age were used. The animals were randomly separated based on postoperative time points: five rabbits at 21 and four at 42 days. A 1-cm segmental bone defect was created in both radii. The bone defects were filled with an F18 bioglass putty. Results: Immediate postoperative radiographic examination revealed the biomaterial occupying the segmental bone defect as a well-defined radiopaque structure with a density close to bone tissue. At 21 and 42 days after surgery, a reduction in radiopacity and volume of the biomaterial was observed, with particle dispersion in the bone defect region. Histologically, the induced membrane was verified in all animals, predominantly composed of fibrocollagenous tissue. In addition, chondroid and osteoid matrices undergoing regeneration, a densely vascularized tissue, and a foreign body type reaction composed of macrophages and multinucleated giant cells were seen. Conclusions: the F18 bioglass putty caused a foreign body-type inflammatory response with the development of an induced membrane without expansion capacity to perform the second stage of the Masquelet technique.

Phlomoides (L.) Moench belongs to the Lamiaceae family. It has recently undergone significant changes in taxonomy, with many species from Eremostachys and Phlomis added to the genus. The aforementioned species were studied in terms of morphological and phytochemical systematics. Species of Phlomoides are distinguished from Phlomis by their densely bearded upper corolla lip and nutlet. However, Eremostachys and Phlomoides have a lot in common morphologically. Plant chemosystematics present iridoids, phenylethanoids, and furanolabdanes as dominant constituents of Phlomoides species. Long-term traditional uses, such as bone fracture therapy, local analgesic, and wound healing actions, pique researchers' interest in these plants. The species and their secondary metabolites have been implicated in drug discovery by their anti-inflammatory and bone-development properties in vitro, in vivo, and clinically. A review of the taxonomic status based on phytochemical and morphological characteristics, as well as the clinical importance of the Phlomoides genus, is presented in the current study to provide a basis for further investigations.

The aim of the study was to analyze the effect of cranberry juice on bone microstructure. The research was carried out on an animal model (experimental animals, Windstar rats). The structure of the proximal tibial metaphysis was analyzed using micro CT, and X-ray microtomography equipment with a VDS 1.3Mp FW camera. It was found that cranberry juice increased bone mineral density (BMD). It also increased the thickness of the bone trabeculae (Tb.Th). The highest BMD value was observed in group drinking a 10% concentration of cranberry juice. In rats drinking 25% concentration, an increase in Tb.Th was observed compared to the two other groups, including the control group. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of a 20-week exercise program on bone mineral parameters in children with overweight or obesity. Randomized controlled trial. This study took part from November 21, 2014, to June 30, 2016, in Granada, Spain. A secondary analysis of this parallel-group randomized controlled trial was performed with 77 children with overweight or obesity (9.9 ± 1.2, 65 % boys) who were randomly allocated to exercise or control group. All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions/week of aerobic plus resistance training for 20 weeks. A whole-body scan by dual-energy X-ray absorptiometry was carried out to obtain body composition at total body less head, arms, lumbar spine, pelvis, and legs. Participants in the exercise group acquired significantly higher total body aBMD (mean z-score [95 % confidence intervals, CI], 0.607 [0.522–0.692]) compared with the participants in the control group (mean z-score, 0.472 [0.388–0.556]); difference between groups, 0.135 standard deviations [95 % CI 0.015–0.255], and legs aBMD (mean z-score, 0.629 [0.550–0.708]); control group (mean z-score, 0.518 [0.440–0.596]); difference between groups, 0.111 [0.001–0.222]; all p < 0.05. There were no significant differences between exercise group and control group at the remaining evaluated regions (p > 0.05). A 20-week non-specifically bone-targeted exercise program induced a small, yet significant, improvement on total body and legs aBMD in children with overweight or obesity. Future studies should investigate the interaction of weight status in the bone response to exercise programs. Prospectively registered in ClinicalTrials.gov Identifier: NCT02295072. [ABSTRACT FROM AUTHOR]

Copyright of Turkiye Klinikleri Journal of Dental Sciences is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone–related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the growing mandibular condyle. In the postnatal MCC of Pthrp mCherry/+ mice, PTHrP-mCherry was specifically expressed by cells in the superficial layer immediately adjacent to RUNX2-expressing cells in the polymorphic layer. PTHrP ligands diffused across the polymorphic and chondrocyte layers where its cognate receptor PTH1R was abundantly expressed. We further analyzed the mandibular condyle of Pthrp mCherry/mCherry mice lacking functional PTHrP protein (PTHrP-KO). At embryonic day (E) 18.5, the condylar process and MCC were significantly truncated in the PTHrP-KO mandible, which was associated with a significant reduction in cell proliferation across the polymorphic layer and a loss of SOX9+ cells in the chondrocyte layers. The PTHrP-KO MCC showed a transient increase in the number of Col10a1+ hypertrophic chondrocytes at E15.5, followed by a significant loss of these cells at E18.5, indicating that superficial layer–derived PTHrP prevents premature chondrocyte exhaustion in the MCC. The expression of Runx2, but not Sp7, was significantly reduced in the polymorphic layer of the PTHrP-KO MCC. Therefore, PTHrP released from cells in the superficial layer directly acts on cells in the polymorphic layer to promote proliferation of chondrocyte precursor cells and prevent their premature differentiation by maintaining Runx2 expression, revealing a unique PTHrP gradient-directed mechanism that regulates MCC chondrogenesis. [ABSTRACT FROM AUTHOR]

The wide distribution of mycotoxins, including aflatoxin B1 and ochratoxin A, in the environment and their influence on living organisms make them an interesting research problem. Numerous complications of intoxication with these substances are known, however, particular attention is paid to the effects on the skeletal and nervous systems. The inflammatory effect, presented by the increase in the concentration of cytokines - IL-6 and TNF-α may influence the immune dysregulation present in bone metabolism disorders, as well as in neurodegeneration. Mycotoxins also contribute to osteodegeneration by modifying vitamin D metabolism. Interestingly, and still unexplored, is the mechanism of intrauterine influence on bone metabolism and neurodegeneration processes. Understanding the above mechanisms may help in monitoring the toxic effects of intoxication with these toxins. It can also help develop methods of therapy for poisoning with this compound, in animals and humans. [ABSTRACT FROM AUTHOR]

Persistent inflammation biologically alters signaling molecules and ultimately affects osteogenic differentiation, including in modern-day broilers with unique physiology. Lipopolysaccharides (LPS) are Gram-negative bacterial components that activate cells via transmembrane receptor activation and other molecules. Previous studies have shown several pathways associated with osteogenic inductive ability, but the pathway has yet to be deciphered, and data related to its dose-dependent effect are limited. Primary mesenchymal stem cells (MSCs) were isolated from the bones of day-old broiler chickens, and the current study focused on the dose-dependent variation (3.125 micrograms/mL to 50 micrograms/mL) in osteogenic differentiation and the associated biomarkers in primary MSCs. The doses in this study were determined using a cell viability (MTT) assay. The study revealed that osteogenic differentiation varied with dose, and the cells exposed to higher doses of LPS were viable but lacked differentiating ability. However, this effect became transient with lower doses, and this phenotypic character was observed with differential staining methods like Alizarin Red, Von Kossa, and alkaline phosphatase. The data from this study revealed that LPS at varying doses had a varying effect on osteogenic differentiation via several pathways acting simultaneously during bone development. [ABSTRACT FROM AUTHOR]

ObjectivesGonadotropin-releasing hormone agonist treatment is important for optimal growth in girls with central precocious puberty (CPP). Data are lacking regarding benefit to height outcome when treatment is started after chronological age (CA) of 7 years, and if continued beyond CA of 10 years or bone age (BA) of 12 years.MethodsForty-eight girls with CPP were treated with monthly leuprolide depot. Change in predicted adult height (PAH) during treatment was assessed. Changes in PAH and growth velocity were compared between girls initiating treatment at CA 5 cm PAH change during treatment was similar, and PAH increased throughout treatment in most girls, regardless of age at treatment initiation. PAH continued to increase in 16/19 girls who continued treatment after BA of 12 years, and also in 16/22 girls who continued treatment after CA of 10 years.ConclusionsPAH improved in most girls who initiated treatment after CA of 7 years. It continued to improve in most girls with longer treatment, even past BA of 12 years or CA of 10 years, which suggests that no absolute CA or BA limit should define initiation or end of treatment. Treatment plans need to be individualized, and neither treatment initiation nor cessation should be based on BA or CA alone.

Wnt signaling executes an indispensable performance in osteoblast differentiation, bone development, homeostasis, and remodeling. Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of β-catenin in the bone environment. Going through the novel discoveries done via high-throughput sequencing technologies on genetic mouse models, we highlighted the significant contribution of Wnt ligands, co-receptors, inhibitors, their related skeletal phenotypes in mouse models and the similar bone disorders clinically observed in human beings. Moreover, the crosstalk between Wnt signaling pathway and BMP, TGF-β, FGF, Hippo, Hedgehog, Notch and PDGF signaling pathways is thoroughly demonstrated to be the underlying gene regulatory network that orchestrates osteoblast differentiation and bone development. We also introspected the significance of Wnt signaling transduction in the reorganization of cellular metabolism by stimulating glycolysis, glutamine catabolism, and fatty acid oxidation in osteoblast-lineage cells that display an important regulatory arbor in the cellular bioenergetics of the bone. Throughout this evaluation, most to date therapeutical approaches towards osteoporosis and other bone maladies found in human beings, are formulated with an aspiration to holistically revamp the present clinical applications involving various monoclonal antibodies therapies that lack specificity, efficacy, and safety into more requisite advanced therapeutics that satisfy these three requirements for further clinical considerations. Conclusively, our review provides comprehensive scientific findings related to the fundamental significance of Wnt signaling cascades in skeletal system and the underlying gene regulatory network with other signaling pathways enlightening researchers with the possibility to further integrate the identified target molecules into therapeutic strategies for skeletal disorders treatment in the clinic.

Abstract Mesenchymal progenitors (MPs) are considered to play vital roles in bone development, growth, bone turnover, and repair. In recent years, benefiting from advanced approaches such as single-cell sequence, lineage tracing, flow cytometry, and transplantation, multiple MPs are identified and characterized in several locations of bone, including perichondrium, growth plate, periosteum, endosteum, trabecular bone, and stromal compartment. However, although great discoveries about skeletal stem cells (SSCs) and progenitors are present, it is still largely obscure how the varied landscape of MPs from different residing sites diversely contribute to the further differentiation of osteoblasts, osteocytes, chondrocytes, and other stromal cells in their respective destiny sites during development and regeneration. Here we discuss recent findings on MPs’ origin, differentiation, and maintenance during long bone development and homeostasis, providing clues and models of how the MPs contribute to bone development and repair.

By 2050, the global population will exceed 9 billion, demanding a 70 % increase in food production. Animal proteins alone may not suffice and contribute to global warming. Alternative proteins such as legumes, algae, and insects are being explored, but their health impacts are largely unknown. For this, three-week-old rats were fed diets containing 20 % protein from various sources for six weeks. A casein-based control diet was compared to soy isolate, spirulina powder, chickpea isolate, chickpea flour, and fly larvae powder. Except for spirulina, alternative protein groups showed comparable growth patterns to the casein group. The Spirulina group demonstrated 17 % lower body weight and 9 % lower body and femur length. Morphological and mechanical tests of femur bones matched growth patterns. Caecal 16S analysis highlighted the impact on gut microbiota diversity. Chickpea flour showed significantly lower α-diversity compared with casein and chickpea isolate groups while chickpea flour, had the greatest distinction in β-diversity. Alternative protein sources supported optimal growth, but quality and health implications require further exploration.