Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation.

SOX8 was linked in a genome-wide association study to human height heritability, but roles in chondrocytes for this close relative of the master chondrogenic transcription factor SOX9 remain unknown. We undertook here to fill this knowledge gap. High-throughput assays demonstrate expression of human SOX8 and mouse Sox8 in growth plate cartilage. In situ assays show that Sox8 is expressed at a similar level as Sox9 in reserve and early columnar chondrocytes and turned off when Sox9 expression peaks in late columnar and prehypertrophic chondrocytes. Sox8-/- mice and Sox8fl/flPrx1Cre and Sox9fl/+Prx1Cre mice (inactivation in limb skeletal cells) have a normal or near normal skeletal size. In contrast, juvenile and adult Sox8fl/flSox9fl/+Prx1Cre compound mutants exhibit a 15 to 20% shortening of long bones. Their growth plate reserve chondrocytes progress slowly toward the columnar stage, as witnessed by a delay in down-regulating Pthlh expression, in packing in columns and in elevating their proliferation rate. SOX8 or SOX9 overexpression in chondrocytes reveals not only that SOX8 can promote growth plate cell proliferation and differentiation, even upon inactivation of endogenous Sox9, but also that it is more efficient than SOX9, possibly due to greater protein stability. Altogether, these findings uncover a major role for SOX8 and SOX9 in promoting skeletal growth by stimulating commitment of growth plate reserve chondrocytes to actively proliferating columnar cells. Further, by showing that SOX8 is more chondrogenic than SOX9, they suggest that SOX8 could be preferred over SOX9 in therapies to promote cartilage formation or regeneration in developmental and degenerative cartilage diseases.

The evolution of the adolescent growth spurt: Urinary biomarkers of bone turnover in wild chimpanzees (Pan troglodytes).

Life history theory addresses how organisms balance development and reproduction. Mammals usually invest considerable energy into growth in infancy, and they do so incrementally less until reaching adult body size, when they shift energy to reproduction. Humans are unusual in having a long adolescence when energy is invested in both reproduction and growth, including rapid skeletal growth around puberty. Although many primates, especially in captivity, experience accelerated growth in mass around puberty, it remains unclear whether this represents skeletal growth. Without data on skeletal growth in nonhuman primates, anthropologists have often assumed the adolescent growth spurt is uniquely human, and hypotheses for its evolution have focused on other uniquely human traits. The lack of data is largely due to methodological difficulties of assessing skeletal growth in wild primates. Here, we use two urinary markers of bone turnover-osteocalcin and collagen-to study skeletal growth in a large, cross-sectional sample of wild chimpanzees (Pan troglodytes) at Ngogo, Kibale National Park, Uganda. For both bone turnover markers, we found a nonlinear effect of age, which was largely driven by males. For male chimpanzees, values for osteocalcin and collagen peaked at age 9.4 years and 10.8 years, respectively, which corresponds to early and middle adolescence. Notably, collagen values increased from 4.5 to 9 years, suggesting faster growth during early adolescence compared to late infancy. Biomarker levels plateaued at 20 years in both sexes, suggesting skeletal growth continues until then. Additional data, notably on females and infants of both sexes, are needed, as are longitudinal samples. However, our cross-sectional analysis suggests an adolescent growth spurt in the skeleton of chimpanzees, especially for males. Biologists should avoid claiming that the adolescent growth spurt is uniquely human, and hypotheses for the patterns of human growth should consider variation in our primate relatives.

Management of a prosthetic complication on an implant restoration placed when the patient was 10 years old: A case report.

The use of dental implants in pediatric patients may create unique complications. A 38-year-old patient presented with a mobile, cement-retained implant crown due to an abutment screw loosening. The maxillary right central incisor implant was placed when the patient was 10 years old. Pus discharge from the peri-implant sulcus was observed. The mucosal margin of the implant was at the level of the mucogingival junction of neighboring teeth. Radiographically, the platform of the implant appeared to be at the level of the apical third of the adjacent roots. After removing the existing implant-retained crown, the inflamed peri-implant tissue covering the implant platform was removed and the stability of the implant was confirmed. A new screw-retained implant crown was made using an angulated screw channel to correct the labiopalatal angulation of the implant and allow for retrievability. Pink porcelain was used to match the mucosal margin of the implant crown to that of the maxillary left central incisor. This case report highlights the risk of implant placement in pediatric patients and agrees with previous reports that implants should be delayed until growth is complete.

Infra- and labio-position of two maxillary central incisor implants in an older adult at a 17-year follow-up.

OBJECTIVE: This report aims to present an infra- and labio-version of the implants relative to the surrounding teeth in an older patient. BACKGROUND: Infra-positioning of dental implants has been sometimes observed in young adults but not in older patients. MATERIALS AND METHODS: Two implants were placed in both central incisor areas in a 63-year-old female patient in 2002. A splinted implant prosthesis was inserted six months later. RESULTS: After 17 years, a deviation in the position of the implant crown on the #21 area was 9.94 mm labially and 4.69 mm apically with respect to the adjacent tooth (#22). The corresponding values of the implant crown on the #11 area were 5.96 and 2.34 mm (with respect to #12), respectively. CONCLUSION: Dental implants in older adults might develop horizontal and vertical discrepancies relative to the neighbouring teeth.

Evaluation of Spheno-occipital Synchondrosis Fusion in Chinese Population Using CBCT: A Cross-sectional Study.

AIM: This study sought to assess the fusion of spheno-occipital synchondrosis (SOS) in Chinese population using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This is a cross-sectional study in which data were randomly collected based on the pre-existing institutional records. Following selection criteria, the CBCT images of 500 patients aged 6-25 years (226 males and 274 females) were analyzed. Three-dimensional virtual models were oriented at a standardized position, then adjusted to the median sagittal plane (MSP) view. A four-stage scoring system was used; completely open, partially fused, semi-fused, or completely fused. The student's t-test, one-way ANOVA, Pearson correlation, and linear regression analysis were used and the significant level was set at ≤0.05. RESULTS: The mean age of closure of stages 1, 2, 3, and 4 were 7.44, 9.62, 12.94, and 19.03 years in females, and 8.79, 11.13, 14.82, and 20.18 years in males, respectively. There was significantly strong positive correlation between spheno-occipital fusion and age (female: r = 0.853, male: r = 0.879; p <0.001), with 1.47 ± 0.33 years earlier fusion in females. All inter- and intra-stages mean ages were statistically significant in both genders. The transition age model demonstrated a mean age (in years) between stages 1-2 (10.1), stages 2-3 (12.79), and stage 3-4 (17.93) for males, and stages 1-2 (8.96), stages 2-3 (11.45), and stage 3-4 (16.69) for females. CONCLUSIONS: The present findings of SOS stages of fusion in both genders could guide age estimation and assessment of normal skeletal growth patterns and active skeletal growth period in the Chinese population. CLINICAL SIGNIFICANCE: There is still controversy about the time to closure of the SOS because of population and assessment technique variations. This study could be used as a reference for the specific examined population during planning for dentofacial orthopedic and/or orthognathic surgery and dental implant prosthesis for both genders. Moreover, these finding may be useful for medical purposes.

Physiological regulation of bone length and skeletal proportion in mammals.

NEW FINDINGS: What is the topic of this review? Mechanisms regulating bone length and skeletal proportions What advances does it highlight? The study of differential bone length between leg and finger bones, metatarsals of the Egyptian jerboa and genomic analysis of giraffes. ABSTRACT: Among mammalian species, skeletal structures vary greatly in size and shape, leading to a dramatic variety of body sizes and proportions. How different bones grow to different lengths, whether among different species, different individuals of the same species, or even in different anatomical parts of our the body, has always been a fascinating subject of research in biology and physiology. In the current review, we focus on some of the recent advances in the field and discuss how these provided important new insights into the mechanisms regulating bone length and skeletal proportions.

Lack of biological mortality bias in the timing of dental formation in contemporary children: Implications for the study of past populations.

OBJECTIVES: Biological mortality bias is the idea that individuals who perish (non-survivors) are biologically distinct from those who survive (survivors). If biological mortality bias is large enough, bioarchaeological studies of nonsurvivors (skeletal samples) cannot accurately represent the experiences of the survivors of that population. This effect is particularly problematic for the study of juvenile individuals, as growth is particularly sensitive to environmental insults. In this study, we test whether biological mortality bias exists in one dimension of growth, namely dental development. MATERIALS AND METHODS: Postmortem computed tomography scans of 206 children aged 12 years and younger at death were collected from two institutions in the United States and Australia. The sample was separated into children dying from natural causes as proxies for non-survivors and from accidental causes as proxies for survivors. Differences in the timing of dental development were assessed using sequential logistic regressions between dental formation stages and residual analysis of dental minus chronological age. RESULTS: No consistent delay in age of attainment of dental stages was documented between survivors and non-survivors. Delays between survivors and non-survivors in dental relative to chronological age were greatest for infants, and were greater for females than for males. DISCUSSION: Lack of biological mortality bias in dental development reinforces confidence in juvenile age estimates and therefore in skeletal growth profiles and growth studies. As dental development is known to be less environmentally sensitive than skeletal growth and development, further studies should examine biological mortality bias in long bone length.

Differences in skeletal growth patterns: an exploratory approach using elliptic Fourier analysis.

OBJECTIVE: Apply elliptic Fourier analysis to find shape differences among the hypodivergent, normodivergent, and hyperdivergent growth patterns in skeletal classes I, II and, III in mandibular and maxillary curves and evaluate the discriminatory capacity of these differences. MATERIALS AND METHODS: A total of 626 adult patients were included: 354 Brazilian patients (52 with tomographic information and 302 with radiographic information) and 272 Colombian patients with radiographic information. Lateral views were selected. The maxillary and mandibular curves were digitized. Elliptic Fourier analysis was employed considering with 20 harmonics as well as filtering size, rotation, and translation properties. One-way non-parametric MANOVA was employed to determine differences. A confusion matrix tool was employed to analyze the discriminatory capacity of the model. RESULTS: Significant shape differences in the mandibular and maxillary contours were found among the hypodivergent, normodivergent, and hyperdivergent growth patterns in classes I, II, and III (p < 0.05). The accuracies obtained from the confusion matrix were respectively 74.1, 79.5, and 90.1% in classes I, II, and III in the mandibular curves and respectively 71.9, 73.9, and 75% in classes I, II, and III in the maxillary curves. CONCLUSIONS: Elliptic Fourier analysis can be used to find shape differences with an acceptable discriminatory capacity, especially in the mandible contour. Maxillary and mandibular bone curves each significantly defined facial biotypes regardless of the size and position properties. CLINICAL RELEVANCE: This exploration offers a way to quantify mandibular morphology for the construction of an economic mandibular prediction system applicable to the Latin American population.

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.

Evaluation of condylar cortical bone thickness in patient groups with different vertical facial dimensions using cone-beam computed tomography.

The aim of this study is to evaluate through computed tomography differences in cortical plate thickness of condyle in patients with a different facial vertical skeletal pattern. The final sample of this retrospective study included CBCT exams of 60 adult subjects (mean age 33.2 ± 5.6), selected from the digital archive of a private practice. The subjects were assigned to 3 different groups according to the values of the Frankfurt-mandibular plane angle: hyper-, normo-, and hypodivergent groups. The volume rendering of the mandible was obtained and three condylar points were marked on it: median pole, lateral pole and the most cranial point. For each considered reference point, the minimum distance between external and internal cortical surface was measured, obtaining three different outcomes: condylar cortical bone thickness of median pole (CCBToMP), lateral pole (CCBToLP) and cranial pole (CCBToCP). The measurements were executed by means of Mimics software by the same expert operator in specific scan views. The cortical bone thickness of hyperdivergent patients was found to be statistically thicker than normodivergent patients and hypodivergent patients. Cortical bone thickness of normodivergent patients was found thicker than hypodivergent patients. All the differences were statistically significant (p < 0.05). The Pearson correlation coefficient showed a statistically significant correlation (p < 0.001) between the Frankfurt-mandibular plane angle and the evaluated cortical bone thickness outcomes. Facial biotype characteristics that define vertical facial skeletal pattern affect the cortical bone thickness of mandibular condyle.

The impact of social experiences of physical and structural violence on the growth of African enslaved children recovered from Lagos, Portugal (15th-17th centuries).

OBJECTIVES: The purpose of this article is to examine the impacts of physical and structural violence on the well-being of early modern enslaved Africans by comparing the growth of children in an archaeological sample recovered from Lagos, Portugal with that of modern children known to have lived under socially oppressive and racist political regimes. MATERIALS AND METHODS: The age of 18 individuals was estimated from the length of developing teeth. Long bone lengths for age in the enslaved African sample were compared with two black juvenile known age samples: the Raymond Dart (South Africa) and Hamann-Todd (United States) collections. Z-scores were calculated for all samples using black children in the South Africa Long Bone (SALB) database as the reference. The similarity of growth across the samples was tested and skeletal growth profiles (SGPs) were devised for the three samples. RESULTS: The children in the Lagos, Raymond Dart, and Hamann-Todd samples were all small for age compared to the SALB reference. While children in the Dart sample tended to be the smallest for age and in the Hamann-Todd the largest, with the children in the Lagos sample falling between them, the three samples did not show significant differences in growth status. DISCUSSION: The growth deficits shown in this study demonstrate the severe impacts of physical and structural violence on the lives of these children. Although uncertainty remains regarding the timing of growth insults relative to arrival, slavery in Portugal as materialized in these individuals was as violent as in other countries.

The INTERGROWTH-21st fetal growth standards: toward the global integration of pregnancy and pediatric care.

The purpose of the INTERGROWTH-21st project was to develop international, prescriptive standards for fetal growth assessed by ultrasound and fundal height, preterm postnatal growth, newborn size and body composition, maternal weight gain, and infant development at the age of 2 years. Hence, we have produced, based on World Health Organization recommendations, the first comprehensive set of international standards of optimal fetal and newborn growth that perfectly match the existing World Health Organization child growth standards. Uniquely, the same population was followed up longitudinally from 9 weeks of fetal life to 2 years of age, with growth, health, and nutritional status assessment at 2 years supporting the appropriateness of the population for construction of growth standards. The resulting package of clinical tools allows, for the first time, growth and development to be monitored from early pregnancy to infancy. The INTERGROWTH-21st fetal growth standards, which are based on observing >4500 healthy pregnancies, nested in a study of >59,000 pregnancies from populations with low rates of adverse perinatal outcomes, show how fetuses should grow-rather than the more limited objective of past references, which describe how they have grown at specific times and locations. Our work has confirmed the fundamental biological principle that variation in human growth across different populations is mostly dependent on environmental, nutritional, and socioeconomic factors. We found that when mothers' nutritional and health needs are met and there are few environmental constraints on growth, <3.5% of the total variability of skeletal growth was due to differences between populations. We propose that not recognizing the concept of optimal growth could deprive the most vulnerable mothers and their babies of optimal care, because local growth charts normalize those at highest risk for growth restriction and overweight, and can be valuable for policymakers to ensure rigorous evaluation and effective resource allocation. We strongly encourage colleagues to join efforts to provide integrated, evidence-based growth monitoring to pregnant women and their infants worldwide. Presently, there are 23.3 million infants born small for gestational age in low- to middle-income countries according to the INTERGROWTH-21st newborn size standards. We suggest that misclassification of these infants by using local charts could affect the delivery of optimal health care.

Bone-specific alkaline phosphatase - a potential biomarker for skeletal growth assessment.

OBJECTIVE: The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages. DESIGN: Cross-sectional study. SETTING: Maulana Azad Institute of Dental Sciences, New Delhi, India. PARTICIPANTS: 150 subjects (75 males and 75 females) in the age group of 8-20 years. METHODS: Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann-Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages. RESULTS: Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p < .01). CONCLUSIONS: BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.

An analysis of dental development in Pleistocene Homo using skeletal growth and chronological age.

OBJECTIVES: This study takes a new approach to interpreting dental development in Pleistocene Homo in comparison with recent modern humans. As rates of dental development and skeletal growth are correlated given age in modern humans, using age and skeletal growth in tandem yields more accurate dental development estimates. Here, I apply these models to fossil Homo to obtain more individualized predictions and interpretations of their dental development relative to recent modern humans. MATERIALS AND METHODS: Proportional odds logistic regression models based on three recent modern human samples (N = 181) were used to predict permanent mandibular tooth development scores in five Pleistocene subadults: Homo erectus/ergaster, Neanderthals, and anatomically modern humans (AMHs). Explanatory variables include a skeletal growth indicator (i.e., diaphyseal femoral length), and chronological age. RESULTS: AMHs Lagar Velho 1 and Qafzeh 10 share delayed incisor development, but exhibit considerable idiosyncratic variation within and across tooth types, relative to each other and to the reference samples. Neanderthals Dederiyeh 1 and Le Moustier 1 exhibit delayed incisor coupled with advanced molar development, but differences are reduced when femoral diaphysis length is considered. Dental development in KNM-WT 15,000 Homo erectus/ergaster, while advanced for his age, almost exactly matches the predictions once femoral length is included in the models. DISCUSSION: This study provides a new interpretation of dental development in KNM-WT 15000 as primarily reflecting his faster rates of skeletal growth. While the two AMH specimens exhibit considerable individual variation, the Neanderthals exhibit delayed incisor development early and advanced molar development later in ontogeny.

Selective protein depletion impairs bone growth and causes liver fatty infiltration in female rats: prevention by Spirulina alga.

Chronic protein malnutrition leads to child mortality in developing countries. Spirulina alga (Spi), being rich in protein and growing easily, is a good candidate as supplementation. We showed that Spi completely prevents bone growth retardation and liver disturbances observed in young rats fed a low protein diet. This supports Spi as a useful source of vegetable protein to fight against protein malnutrition. INTRODUCTION: Chronic malnutrition is a main factor of child mortality in developing countries. A low protein diet impairs whole-body growth and leads to fatty liver in growing rats. Spi has great potential as a supplementation as it has a 60 % protein content and all essential amino acids. However, its specific impact on bone growth and the related secretion of hepatokines have not yet been studied. METHODS: To address this question, 6-week-old female rats were fed isocaloric diets containing 10 % casein, 5 % casein, or 5 % casein + 5 % protein from Spi during 9 weeks. Changes in tibia geometry, microarchitecture, BMC, BMD, and biomechanical properties were analyzed. Serum IGF-I, FGF21, follistatin, and activin A were assessed as well as their hepatic gene expressions in addition to those of Sirt1, Ghr, and Igf1r. Hepatic fat content was also assessed. RESULTS: A low protein diet altered bone geometry and reduced proximal tibia BMD and trabecular bone volume. In addition, it increased hepatic fat content and led to hepatic GH resistance by decreasing serum IGF-I and increasing serum FGF21 without altering serum activin A and follistatin. Spi prevented low protein diet-induced bone, hepatic, and hormonal changes, and even led to higher biomechanical properties and lower hepatic fat content in association with specific InhbA and Follistatin expression changes vs. the 10 % casein group. CONCLUSIONS: Altogether our results demonstrate the preventive impact of Spi on bone growth delay and hepatic GH resistance in conditions of isocaloric dietary protein deficiency.

Calcium Plus Vitamin D Supplementation During the Third Trimester of Pregnancy in Adolescents Accustomed to Low Calcium Diets Does Not Affect Infant Bone Mass at Early Lactation in a Randomized Controlled Trial.

BACKGROUND: Pregnancy and lactation in adolescents with low calcium intake may impair fetal growth and infant bone mass. OBJECTIVE: We investigated the effects of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers consuming low calcium diets (∼600 mg/d) on fetal biometry and infant bone mass, and the relation between infant and maternal bone mass during early lactation. METHODS: Infants of mothers who received calcium (600 mg/d) plus cholecalciferol (200 IU/d) supplementation (n = 30) or placebo (n = 26) from 26 wk of gestation until parturition were studied. Fetal biometric measurements at 23 and 36 wk of gestation were obtained from medical records. Infant anthropometric and total body bone measurements [bone mineral content (BMC), bone area (BA), and bone mineral density (BMD)] at 5 wk postpartum were assessed by dual-energy X-ray absorptiometry. Maternal BMD z scores for total body, lumbar spine, total hip, and femoral neck at 5 wk postpartum were obtained. Group comparisons were adjusted for significant covariates. RESULTS: Maternal mean serum 25-hydroxyvitamin D was 59 nmol/L at baseline in both groups. No differences in fetal measurements at 36 wk of gestation were observed between the groups, except for body weight and its increment from 23 to 36 wk, which were higher in the supplemented group (6.8%, P = 0.014 and 10.5%, P = 0.07, respectively). Infant BMC (61.1 ± 21.7 g), BA (167 ± 79 cm(2)), and BMD (0.385 ± 0.069 g/cm(2)) did not significantly differ between the groups. In the placebo group, infant BMC and BA were negatively correlated with maternal BMD z scores for total body (r = -0.40 and r = -0.47; P < 0.05) and hip (r = -0.41 and r = -0.46; P < 0.05). In contrast, no correlations were observed in the supplemented group. CONCLUSIONS: Calcium and vitamin D supplementation of the adolescents studied resulted in higher fetal body weight at 36 wk of gestation and had no effect on infant bone mass at 5 wk postpartum. Because correlations between maternal and infant bone mass were evident only in the placebo group, infant bone mass appeared to be more dependent on maternal skeletal mass when calcium intake was low. This trial was registered at clinicaltrials.gov as NCT01732328.

Investigating femoral growth disruption in subadults from the 10th-13th century St. Étienne cemetery of Toulouse, France.

OBJECTIVES: The skeleton embodies an individual's environment and lived experiences. Studying childhood growth disruption can, therefore, aid in understanding the experiences of children in the past. This study evaluates growth disruption in a medieval Toulousian subadult sample to explore factors that may have influenced childhood growth and mortality at this site and to assess the utility of Harris line (HL) interpretations in bioarchaeology. MATERIALS AND METHODS: Femoral growth disruption was assessed in n = 71 subadults (0.125-12.42 years) from the 10th-13th century St. Étienne cemetery of Toulouse, France, using femoral length, total area, cortical area, and relative cortical area. Femoral radiographs were assessed for HLs. To determine the prevalence of growth disruption, z-scores were calculated using data from the Denver growth study. RESULTS: The majority of subadults in this sample suffered from femoral growth disruption. Young children (1.0-3.99 years) were the most affected, with >65% experiencing reduced appositional growth and linear growth stunting at time-of-death. Additionally, while many individuals presented with observable HLs, linear and appositional growth did not significantly differ between individuals with and without HLs. DISCUSSION: Maternal malnutrition and inadequate complementary feeding practices likely contributed to the high prevalence of growth disruption among the youngest individuals in the study. The older children and adolescents buried at St. Étienne experienced an amelioration in growth deficits, indicating an improvement in nutrition and/or disease load. The results of this study suggest that more consideration is required when interpreting the presence/absence of HLs, and that studies assessing HLs may benefit from using a more individualistic approach.

Lysine-rich rice partially enhanced the growth and development of skeletal system with better skeletal microarchitecture in young rats.

Rice is the primary staple food for half of the world's population but is low in lysine content. Previously, we developed transgenic rice with enhanced free lysine content in rice seeds (lysine-rich rice), which was shown safe for consumption and improved the growth in rats. However, the effects of lysine-rich rice on skeletal growth and development remained unknown. In this study, we hypothesized that lysine-rich rice improved skeletal growth and development in weaning rats. Male weaning Sprague-Dawley rats received lysine-rich rice (HFL) diet, wild-type rice (WT) diet, or wild-type rice with various contents of lysine supplementation diet for 70 days. Bone microarchitectures were examined by microcomputed tomography, bone strength was investigated by mechanical test, and dynamics of bone growth were examined by histomorphometric analysis. In addition, we explored the molecular mechanism of lysine and skeletal growth through biochemical testing of growth hormone, bone turnover marker, and amino acid content of rat serum analysis, as well as in a cell culture system. Results indicated that the HFL diet improved rats' bone growth, strength, and microarchitecture compared with the WT diet group. In addition, the HFL diet increased the serum essential amino acids, growth hormone (insulin-like growth factor-1), and bone formation marker concentrations. The cell culture model showed that lysine deficiency reduced insulin-like growth factor-1 and Osterix expression, Akt/mammalian target of rapamycin signaling, and matrix mineralization, and inhibited osteoblast differentiation associated with bone growth. Our findings showed that lysine-rich rice improved skeletal growth and development in weaning rats. A further increase of rice lysine content is highly desirable to fully optimize bone growth and development.

Gestational intermittent hypoxia reduces mandibular growth with decreased Sox9 expression and increased Hif1a expression in male offspring rats.

Introduction: Maternal obstructive sleep apnea (OSA) during pregnancy is the risk factor for impaired fetal growth with low birth weight in the offspring. However, it is unclear whether gestational intermittent hypoxia (IH, a hallmark of maternal OSA) has long-term detrimental consequences on the skeletal development of offspring. This study aimed to investigate postnatal maxillofacial bone growth and cartilage metabolism in male and female offspring that were exposed to gestational IH. Methods: Mother rats underwent IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) for 8 h per day during gestational days (GD) 7-20, and their male and female offspring were analyzed postnatally at 5 and 10 weeks of age. All male and female offspring were born and raised under normoxic conditions. Results: There was no significant difference in whole-body weight and tibial length between the IH male/female offspring and their control counterparts. In contrast, the mandibular condylar length was significantly shorter in the IH male offspring than in the control male offspring at 5 and 10 weeks of age, while there was no significant difference in the female offspring. Real-time polymerase chain reaction (PCR) showed that gestational IH significantly downregulated the mRNA level of SOX9 (a chondrogenesis marker) and upregulated the mRNA level of HIF-1α (a hypoxia-inducible factor marker) in the mandibular condylar cartilage of male offspring, but not in female offspring. Conclusion: Gestational IH induced underdeveloped mandibular ramus/condyles and reduced mRNA expression of SOX9, while enhancing mRNA expression of HIF-1α in a sex-dependent manner.

Molecular and Cellular Characterization of the TH Pathway in the Sea Urchin Strongylocentrotus purpuratus.

Thyroid Hormones (THs) are a class of signaling molecules produced by coupling iodine with tyrosine residues. In vertebrates, extensive data support their important role in a variety of processes such as metabolism, development and metamorphosis. On the other hand, in invertebrates, the synthesis and role of the THs have been, so far, poorly investigated, thus limiting our understanding of the function and evolution of this important animal signaling pathway. In sea urchins, for example, while several studies focused on the availability and function of external sources of iodotyrosines, preliminary evidence suggests that an endogenous TH pathway might be in place. Here, integrating available literature with an in silico analysis, various homologous genes of the vertebrate TH molecular toolkit have been identified in the sea urchin Strongylocentrotus purpuratus. They include genes involved in the synthesis (Sp-Pxdn), metabolism (Sp-Dios), transport (Sp-Ttrl, Sp-Mct7/8/10) and response (Sp-Thr, Sp-Rxr and Sp-Integrin αP) to thyroid hormones. To understand the cell type(s) involved in TH synthesis and/or response, we studied the spatial expression of the TH toolkit during urchin development. Exploiting single-cell transcriptomics data in conjunction with in situ hybridization and immunohistochemistry, we identified cell types that are potentially producing or responding to THs in the sea urchin. Finally, growing sea urchin embryos until the larva stage with and without a source of inorganic iodine, we provided evidence that iodine organification is important for larval skeleton growth.