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Skeletal Growth (skeletal + growth)
Selected AbstractsEstrogen Receptor-, Inhibits Skeletal Growth and Has the Capacity to Mediate Growth Plate Fusion in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2004AS Chagin Abstract To determine the long-term role of ER, in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Our results show that ER, inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. Introduction: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER),,/, and the ER,,/,,,/,, but not the ER,,/,, mouse models have clearly increased serum levels of estradiol. Materials and Methods: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Results: Young adult (4-month-old) ER,,/, mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER, inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER,,/, mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER,,/, mice, must be mediated through ER, because old ER,,/,,,/, mice displayed unchanged, unfused growth plates. Conclusions: Our results confirm that ER, is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER,, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice. [source] Collagen Metabolism Is Markedly Altered in the Hypertrophic Cartilage of Growth Plates from Rats with Growth Impairment Secondary to Chronic Renal FailureJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001Jesús Álvarez Abstract Skeletal growth depends on growth plate cartilage activity, in which matrix synthesis by chondrocytes is one of the major processes contributing to the final length of a bone. On this basis, the present work was undertaken to ascertain if growth impairment secondary to chronic renal insufficiency is associated with disturbances of the extracellular matrix (ECM) of the growth plate. By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collagenase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) and sham-operated rats pair-fed with NX (SPF). NX rats were severely uremic, as shown by markedly elevated serum concentrations of urea nitrogen, and growth retarded, as shown by significantly decreased longitudinal bone growth rates. NX rats showed disturbances in the normal pattern of chondrocyte differentiation and in the rates and degree of substitution of hypertrophic cartilage with bone, which resulted in accumulation of cartilage at the hypertrophic zone. These changes were associated with an overall decrease in the expression of types II and X collagens, which was especially marked in the abnormally extended zone of the hypertrophic cartilage. Unlike collagen, the expression of collagenase-3 was not disturbed severely. Electron microscopic analysis proved that changes in gene expression were coupled to alterations in the mineralization as well as in the collagen fibril architecture at the hypertrophic cartilage. Because the composition and structure of the ECM have a critical role in regulating the behavior of the growth plate chondrocytes, results obtained are consistent with the hypothesis that alteration of collagen metabolism in these cells could be a key process underlying growth retardation in uremia. [source] Skeletal Growth Acceleration with Growth Hormone Secretagogues in Transgenic Growth Retarded Rats: Pattern-Dependent Effects and Mechanisms of DesensitizationJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2001T. Wells Abstract The transgenic growth retarded (Tgr) rat is the first genetic model of growth hormone (GH) deficiency whose growth can be accelerated with exogenous GH secretagogues (GHSs). In this study, we have demonstrated that GHS-receptor (GHS-R) mRNA expression in the arcuate nucleus of Tgr rats was not significantly different to that in wild-type littermates. We have confirmed that GHS-induced elevation in body weight gain was accompanied by acceleration of skeletal growth, and that the effects of the GHS, GHRP-6, were both dose- and pattern-dependent. The growth response with continuous infusion of GHRP-6 was transient, accompanied by suppression of GH and corticosterone responses to bolus injection of GHRP-6. This desensitization occurred without downregulation of arcuate GHS-R mRNA expression, but was accompanied by elevated periventricular somatostatin mRNA expression. In contrast, pulsatile (3-hourly) infusion of GHRP-6 produced sustained growth and GH responses, which were accompanied by suppression of corticosterone responses and elevated arcuate GH-releasing factor (GRF) mRNA expression. Skeletal growth was further accelerated by coinfusion of GRF, but significant depletion of pituitary GH stores suggested that this growth rate may not be sustainable. These experiments confirm the importance of the Tgr rat for investigating the growth promoting potential of the GHSs in the context of GH-deficient dwarfism, and suggest that elevated somatostatin expression may mediate the suppression of the GRF-GH and hypothalamo-pituitary-adrenal axes following continuous GHRP-6 treatment. [source] Conservative treatment of paediatric mandibular fracture by the use of orthodontic appliance and rubber elastics: report of a caseDENTAL TRAUMATOLOGY, Issue 1 2005Petter J. E. Gawelin Abstract,,, Treatment principles of paediatric mandibular fractures may differ from the treatment of the adult population in that a conservative approach is in most cases advocated before the use of internal rigid fixation with plates and screws. This is because of a relative high risk of disturbed facial skeletal growth and risk of damaging unerupted teeth. Knowledge of conservative treatment options is essential in order to minimize these risks and one option is presented in this paper. This case report describes a 5-year-old girl that sustained an open fracture of the mandible and who was successfully treated by the means of applying orthodontic brackets and an arch bar combined with ligatures and rubber elastics. [source] Ammonium perchlorate effects on thyroid function and growth in bobwhite quail chicksENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2004F. M. ANNE Mcnabb Abstract Bobwhite quail chicks were used to investigate ammonium perchlorate (AP; NH4ClO4) effects on thyroid function and growth. Beginning at 3 to 4 d posthatch, we evaluated organismal thyroid status (circulating hormones), activation of the hypo-thalamic-pituitary-thyroid axis (thyroid wt) and thyroidal hormone content over a wide range of AP concentrations (50 ,g/L , 4,000 mg/L) in drinking water, for relatively short (2-week) and longer (8-week) exposures. Thyroidal thyroxine (T4) content, the most sensitive index of decreased thyroid function, decreased markedly in response to increasing perchlorate exposure. Thyroid weight and plasma T4 were less sensitive indicators and similar in their ability to detect thyroid changes. Growth measurements (body wt and skeletal growth) were very insensitive indices. Because thyroids contain large hormone stores, with low exposures or short time periods, these stores can be used to maintain circulating hormones, at least temporarily. Most depletion of thyroidal T4 occurred during the first two weeks of AP exposure. Subsequent decreases were at a slower rate presumably because thyrotropin stimulation of the thyroids at least partially compensated for some of the perchlorate effect. Additional studies of the interactions between AP concentration and exposure time are needed for understanding the complex nature of thyroid responses to perchlorate. [source] Hypertrophy and physiological death of equine chondrocytes in vitroEQUINE VETERINARY JOURNAL, Issue 6 2007Y. A. Ahmed Summary Reasons for performing study: Equine osteochondrosis results from a failure of endochondral ossification during skeletal growth. Endochondral ossification involves chondrocyte proliferation, hypertrophy and death. Until recently no culture system was available to study these processes in equine chondrocytes. Objective: To optimise an in vitro model in which equine chondrocytes can be induced to undergo hypertrophy and physiological death as seen in vivo. Methods: Chondrocytes isolated from fetal or older (neonatal, growing and mature) horses were cultured as pellets in 10% fetal calf serum (FCS) or 10% horse serum (HS). The pellets were examined by light and electron microscopy. Total RNA was extracted from the pellets, and quantitative PCR carried out to investigate changes in expression of a number of genes regulating endochondral ossification. Results: Chondrocytes from fetal foals, grown as pellets, underwent hypertrophy and died by a process morphologically similar to that seen in vivo. Chondrocytes from horses age >5 months did not undergo hypertrophy in pellet culture. They formed intramembranous inclusion bodies and the cultures included cells of osteoblastic appearance. Pellets from neonatal foals cultured in FCS resembled pellets from older horses, however pellets grown in HS underwent hypertrophy but contained inclusion bodies. Chondrocytes from fetal foals formed a typical cartilage-like tissue grossly and histologically, and expressed the cartilage markers collagen type II and aggrecan mRNA. Expression of Sox9, collagen type II, Runx2, matrix metalloproteinase-13 and connective tissue growth factor mRNA increased at different times in culture. Expression of fibroblast growth factor receptor-3 and vascular endothelial growth factor mRNA decreased with time in culture. Conclusions: Freshly isolated cells from fetal growth cartilage cultured as pellets provide optimal conditions for studying hypertrophy and death of equine chondrocytes. Potential relevance: This culture system should greatly assist laboratory studies aimed at elucidating the pathogenesis of osteochondrosis. [source] Longitudinal development of equine conformation from weanling to age 3 years in the ThoroughbredEQUINE VETERINARY JOURNAL, Issue 7 2004T. M. ANDERSON Summary Reasons for performing study: There is little information available to define conformational changes with age using an objective but practical method of recording specific body measurements. Objective: To analyse conformation objectively in a population of racing Thoroughbreds and describe the changes from weanling to age 3 years. Methods: Annual photographs were taken over 4 years and conformation measurements made from photographs using specific reference points marked on the horses. Results: Correlation analysis revealed highly significant, moderate to strong relationships between long bone lengths and wither height for all ages. All long bone lengths showed moderate to strong relationships with each other for all ages. The front and rear pastern angles were significantly correlated with the angle of the dorsal surface of the front and rear hooves, respectively, for all. Wither height, croup height and length of neck topline, neck bottomline, scapula, humerus, radius and femur increased significantly from age 0,1 year and age 1,2 years. Hoof lengths (medial and lateral, right and left) grew significantly between the ages of 0 and 1 and 1 and 2 years, but decreased in length between age 2 and 3 years. Horses became more offset in the right limb between weanling and age 3 years, but the offset ratios did not change with age on the left limb. The angle of the scapula (I), shoulder and radiometacarpus significantly increased between all age groups (became more upright). The angle of the dorsal surface of the hooves (both front and hind) decreased significantly from ages 0 to 1 and 1 to 2 years, but showed no significant difference between ages 2 and 3 years. Conclusions: A strong relationship between long bone lengths and wither height for all ages supports the theory that horses are proportional. Longitudinal bone growth in the distal limb increased only 5,7% from weanling to age 3 years and is presumably completed prior to the yearling year. Several growth measures increased from ages 0 to 1 and 1 to 2 years, but did not increase from age 2,3 years; indicating that growth rate either showed or reached a plateau at this time. Potential relevance: This study provides objective information regarding conformation and skeletal growth in the Thoroughbred which can be utilised for selection and recognition of significant conformational abnormalities. [source] Life-long protein malnutrition in the rat (Rattus norvegicus) results in altered patterns of craniofacial growth and smaller individualsJOURNAL OF ANATOMY, Issue 6 2006Shannon L. Lobe Abstract Dietary protein is a limiting factor in mammalian growth, significantly affecting the non-linear trajectories of skeletal growth. Young females may be particularly vulnerable to protein malnutrition if the restriction is not lifted before they become reproductive. With such early malnutrition, limited amino acids would be partitioned between two physiological objectives, successful reproduction vs. continued growth. Thus, the consequences of protein malnutrition could affect more than one generation. However, few studies have quantified these cross-generational effects. Our objective was to test for differences in skeletal growth in a second generation of malnourished rats compared with rats malnourished only post-weaning, the first generation and with controls. In this longitudinal study we modelled the growth of 22 craniofacial measurements with the logistic Gompertz equation, and tested for differences in the equation's parameters among the diet groups. The female offspring of post-weaning malnourished dams did not catch up in size to the first generation or to controls, although certain aspects of their craniofacial skeleton were less affected than others. The second generation's growth trajectories resembled the longer and slower growth of the first malnourished generation. There was a complex interaction between developmental processes and early nutritional environment, which affected variation of adult size. [source] Exercise When Young Provides Lifelong Benefits to Bone Structure and Strength,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007Stuart J Warden PT Abstract Short-term exercise in growing rodents provided lifelong benefits to bone structure, strength, and fatigue resistance. Consequently, exercise when young may reduce the risk for fractures later in life, and the old exercise adage of "use it or lose it" may not be entirely applicable to the skeleton. Introduction: The growing skeleton is most responsive to exercise, but low-trauma fractures predominantly occur in adults. This disparity has raised the question of whether exercised-induced skeletal changes during growth persist into adulthood where they may have antifracture benefits. This study investigated whether brief exercise during growth results in lifelong changes in bone quantity, structure, quality, and mechanical properties. Materials and Methods: Right forearms of 5-week-old Sprague-Dawley rats were exercised 3 days/week for 7 weeks using the forearm axial compression loading model. Left forearms were internal controls and not exercised. Bone quantity (mineral content and areal density) and structure (cortical area and minimum second moment of area [IMIN]) were assessed before and after exercise and during detraining (restriction to home cage activity). Ulnas were removed after 92 weeks of detraining (at 2 years of age) and assessed for bone quality (mineralization) and mechanical properties (ultimate force and fatigue life). Results: Exercise induced consistent bone quantity and structural adaptation. The largest effect was on IMIN, which was 25.4% (95% CI, 15.6,35.3%) greater in exercised ulnas compared with nonexercised ulnas. Bone quantity differences did not persist with detraining, whereas all of the absolute difference in bone structure between exercised and nonexercised ulnas was maintained. After detraining, exercised ulnas had 23.7% (95% CI, 13.0,34.3%) greater ultimate force, indicating enhanced bone strength. However, exercised ulnas also had lower postyield displacement (,26.4%; 95% CI, ,43.6% to ,9.1%), indicating increased brittleness. This resulted from greater mineralization (0.56%; 95% CI, 0.12,1.00%), but did not influence fatigue life, which was 10-fold greater in exercised ulnas. Conclusions: These data indicate that exercise when young can have lifelong benefits on bone structure and strength, and potentially, fracture risk. They suggest that the old exercise adage of "use it or lose it" may not be entirely applicable to the skeleton and that individuals undergoing skeletal growth should be encouraged to perform impact exercise. [source] An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2005Pierre J. Marie Ph.D. Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15,25 per group) were sham operated or ovariectomized (OVX) and treated with 17,-estradiol (E2, 10 ,g/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30,36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats. In contrast to this inhibitory effect on bone resorption, the osteoid surface, osteoblast surface, mineral apposition rate, and bone formation rate were as high in OVX rats treated with S12911 as in untreated OVX rats. In addition, plasma osteocalcin (OC) and alkaline phosphatase (ALP) levels remained elevated or were further increased in OVX rats treated with S12911. In contrast, treatment with E2 reduced both bone resorption and formation and plasma ALP and OC to the levels in sham rats. The data indicate that the divalent strontium salt S12911 is acting as an uncoupling agent that can prevent the femoral osteopenia and partially prevent the trabecular bone loss in E2-deficient rats by inhibiting bone resorption without reducing bone formation. [source] Estrogen Receptor-, Inhibits Skeletal Growth and Has the Capacity to Mediate Growth Plate Fusion in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2004AS Chagin Abstract To determine the long-term role of ER, in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Our results show that ER, inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. Introduction: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER),,/, and the ER,,/,,,/,, but not the ER,,/,, mouse models have clearly increased serum levels of estradiol. Materials and Methods: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Results: Young adult (4-month-old) ER,,/, mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER, inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER,,/, mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER,,/, mice, must be mediated through ER, because old ER,,/,,,/, mice displayed unchanged, unfused growth plates. Conclusions: Our results confirm that ER, is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER,, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice. [source] Effects of Liver-Derived Insulin-Like Growth Factor I on Bone Metabolism in Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002Klara Sjögren Abstract Insulin-like growth factor (IGF) I is an important regulator of both skeletal growth and adult bone metabolism. To better understand the relative importance of systemic IGF-I versus locally expressed IGF-I we have developed a transgenic mouse model with inducible specific IGF-I gene inactivation in the liver (LI-IGF-I,/,). These mice are growing normally up to 12 weeks of age but have a disturbed carbohydrate and lipid metabolism. In this study, the long-term effects of liver-specific IGF-I inactivation on skeletal growth and adult bone metabolism were investigated. The adult (week 8,55) axial skeletal growth was decreased by 24% in the LI-IGF-I,/, mice whereas no major reduction of the adult appendicular skeletal growth was seen. The cortical cross-sectional bone area, as measured in the middiaphyseal region of the long bones, was decreased in old LI-IGF-I,/, mice. This reduction in the amount of cortical bone was caused mainly by decreased periosteal circumference and was associated with a weaker bone determined by a decrease in ultimate load. In contrast, the amount of trabecular bone was not decreased in the LI-IGF-I,/, mice. DNA microarray analysis of 30-week-old LI-IGF-I,/, and control mice indicated that only four genes were regulated in bone whereas ,40 genes were regulated in the liver, supporting the hypothesis that liver-derived IGF-I is of minor importance for adult bone metabolism. In summary, liver-derived IGF-I exerts a small but significant effect on cortical periosteal bone growth and on adult axial skeletal growth while it is not required for the maintenance of the trabecular bone in adult mice. [source] Calcium Accretion in Girls and Boys During Puberty: A Longitudinal AnalysisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2000Donald A. Bailey Abstract The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BMC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226,651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194,520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199,574 mg/day) and 284 mg/day for girls (58 mg/day; 171,459 mg/day). These longitudinal results are 27,34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium. [source] Skeletal Growth Acceleration with Growth Hormone Secretagogues in Transgenic Growth Retarded Rats: Pattern-Dependent Effects and Mechanisms of DesensitizationJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2001T. Wells Abstract The transgenic growth retarded (Tgr) rat is the first genetic model of growth hormone (GH) deficiency whose growth can be accelerated with exogenous GH secretagogues (GHSs). In this study, we have demonstrated that GHS-receptor (GHS-R) mRNA expression in the arcuate nucleus of Tgr rats was not significantly different to that in wild-type littermates. We have confirmed that GHS-induced elevation in body weight gain was accompanied by acceleration of skeletal growth, and that the effects of the GHS, GHRP-6, were both dose- and pattern-dependent. The growth response with continuous infusion of GHRP-6 was transient, accompanied by suppression of GH and corticosterone responses to bolus injection of GHRP-6. This desensitization occurred without downregulation of arcuate GHS-R mRNA expression, but was accompanied by elevated periventricular somatostatin mRNA expression. In contrast, pulsatile (3-hourly) infusion of GHRP-6 produced sustained growth and GH responses, which were accompanied by suppression of corticosterone responses and elevated arcuate GH-releasing factor (GRF) mRNA expression. Skeletal growth was further accelerated by coinfusion of GRF, but significant depletion of pituitary GH stores suggested that this growth rate may not be sustainable. These experiments confirm the importance of the Tgr rat for investigating the growth promoting potential of the GHSs in the context of GH-deficient dwarfism, and suggest that elevated somatostatin expression may mediate the suppression of the GRF-GH and hypothalamo-pituitary-adrenal axes following continuous GHRP-6 treatment. [source] Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trialPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 1 2010Edgardo Abalos Summary Abalos E, Merialdi M, Wojdyla D, Carroli G, Campodónico L, Yao S-E, Gonzalez R, Deter R, Villar J, Van Look P. Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trial. Paediatric and Perinatal Epidemiology 2010; 24: 53,62. Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at <20 weeks gestation) to either placebo (n = 230) or calcium supplements (1500 mg calcium/day in 3 divided doses; n = 231). Growth parameters in utero were assessed with serial ultrasound scans. Birthweight, length, head, abdominal and thigh circumferences were recorded at delivery. No differences were found in fetal biometric measurements recorded at 20, 24, 28, 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not. Similarly, neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups. We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth. [source] Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measuresAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2006H.Y. Handoko The association between vitamin D levels and skeletal growth has long been recognized. However, exposure to low levels of vitamin D during early life is also known to alter brain development, and is a candidate risk factor for schizophrenia. This study examines the association between four polymorphisms in the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three anthropometric variables (height, head size, and head shape). Four single-nucleotide polymorphisms (SNPs; rs10735810/FokI, rs1544410/BsmI, rs7975232/ApaI, and rs731236/TaqI) in the VDR gene were genotyped in 179 individuals with schizophrenia and 189 healthy controls. No significant associations were detected between any of the four VDR SNPs and risk of schizophrenia. Patients were slightly but significantly shorter compared to controls. Of the four SNPs, only rs10735810/FokI was associated with any of the anthropometric measures: the M4 isoform of this SNP was significantly associated with larger head size (P = 0.002). In light of the evidence demonstrating a role for vitamin D during brain development, the association between polymorphisms in VDR and brain development warrants closer scrutiny. Am. J. Hum. Biol. 18:415,417, 2006. © 2006 Wiley-Liss, Inc. [source] Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestationTHE JOURNAL OF PHYSIOLOGY, Issue 9 2008Alison J. Forhead Leptin is an important regulator of appetite and energy expenditure in adulthood, although its role as a nutritional signal in the control of growth and metabolism before birth is poorly understood. This study investigated the effects of leptin on growth, carbohydrate metabolism and insulin signalling in fetal sheep. Crown,rump length-measuring devices and vascular catheters were implanted in 12 sheep fetuses at 105,110 days of gestation (term 145 ± 2 days). The fetuses were infused i.v. either with saline (0.9% NaCl; n= 6) or recombinant ovine leptin (0.5,1.0 mg kg,1 day,1; n= 6) for 5 days from 125 to 130 days when they were humanely killed and tissues collected. Leptin receptor mRNA and protein were expressed in fetal liver, skeletal muscle and perirenal adipose tissue. Throughout infusion, plasma leptin in the leptin-infused fetuses was 3- to 5-fold higher than in the saline-infused fetuses, although plasma concentrations of insulin, glucose, lactate, cortisol, catecholamines and thyroid hormones did not differ between the groups. Leptin infusion did not affect linear skeletal growth or body, placental and organ weights in utero. Hepatic glycogen content and activities of the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the leptin-infused fetuses were lower than in the saline-infused fetuses by 44, 48 and 36%, respectively; however, there were no differences in hepatic glycogen synthase activity or insulin signalling protein levels. Therefore, before birth, leptin may inhibit endogenous glucose production by the fetal liver when adipose energy stores and transplacental nutrient delivery are sufficient for the metabolic needs of the fetus. These actions of leptin in utero may contribute to the development of neonatal hypoglycaemia in macrosomic babies of diabetic mothers. [source] Akt1 in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditionsARTHRITIS & RHEUMATISM, Issue 3 2010Atsushi Fukai Objective To examine the role of the phosphoinositide-dependent serine/threonine protein kinase Akt1 in chondrocytes during endochondral ossification. Methods Skeletal phenotypes of homozygous Akt1-deficient (Akt1,/,) mice and their wild-type littermates were compared in radiologic and histologic analyses. An experimental osteoarthritis (OA) model was created by surgically inducing instability in the knee joints of mice. For functional analyses, we used primary costal and articular chondrocytes from neonatal mice and mouse chondrogenic ATDC5 cells with retroviral overexpression of constitutively active Akt1 or small interfering RNA (siRNA) for Akt1. Results Among the Akt isoforms (Akt1, Akt2, and Akt3), Akt1 was the most highly expressed in chondrocytes, and the total level of Akt protein was decreased in Akt1,/, chondrocytes, indicating a dominant role of Akt1. Akt1,/, mice exhibited dwarfism with normal proliferative and hypertrophic zones but suppressed cartilage calcification in the growth plate compared with their wild-type littermates. In mice with surgically induced OA, calcified osteophyte formation, but not cartilage degradation, was prevented in the Akt1,/, joints. Calcification was significantly suppressed in cultures of Akt1,/, chondrocytes or ATDC5 cells overexpressing siRNA for Akt1 and was enhanced in ATDC5 cells overexpressing constitutively active Akt1. Neither proliferation nor hypertrophic differentiation was affected by the gain or loss of function of Akt1. The expression of ANK and nucleotide pyrophosphatase/phosphodiesterase 1, which accumulate pyrophosphate, a crucial calcification inhibitor, was enhanced by Akt1 deficiency or siRNA for Akt1 and was suppressed by constitutively active Akt1. Conclusion Our findings indicate that Akt1 in chondrocytes controls cartilage calcification by inhibiting pyrophosphate during endochondral ossification in skeletal growth and during osteophyte formation in OA. [source] Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type x collagen geneARTHRITIS & RHEUMATISM, Issue 1 2009Akiro Higashikawa Objective Type X collagen and runt-related transcription factor 2 (RUNX-2) are known to be important for chondrocyte hypertrophy during skeletal growth and repair and development of osteoarthritis (OA) in mice. Aiming at clinical application, this study was undertaken to investigate transcriptional regulation of human type X collagen by RUNX-2 in human cells. Methods Localization of type X collagen and RUNX-2 was determined by immunohistochemistry, and their functional interaction was examined in cultured mouse chondrogenic ATDC-5 cells. Promoter activity of the human type X collagen gene (COL10A1) was examined in human HeLa, HuH7, and OUMS27 cells transfected with a luciferase gene containing a 4.5-kb promoter and fragments. Binding to RUNX-2 was examined by electrophoretic mobility shift assay and chromatin immunoprecipitation. Results RUNX-2 and type X collagen were co-localized in mouse limb cartilage and bone fracture callus. Gain and loss of function of RUNX-2 revealed that RUNX-2 is essential for type X collagen expression and terminal differentiation of chondrocytes. Human COL10A1 promoter activity was enhanced by RUNX-2 alone and more potently by RUNX-2 in combination with the coactivator core-binding factor , in all 3 human cell lines examined. Deletion, mutagenesis, and tandem repeat analyses identified the core responsive element as the region between ,89 and ,60 bp (termed the hypertrophy box [HY box]), which showed specific binding to RUNX-2. Other putative RUNX-2 binding motifs in the human COL10A1 promoter did not respond to RUNX-2 in human cells. Conclusion Our findings indicate that the HY box is the core element responsive to RUNX-2 in human COL10A1 promoter. Studies on molecular networks related to RUNX-2 and the HY box will lead to treatments of skeletal growth retardation, bone fracture, and OA. [source] Heterotrophy in Tropical Scleractinian CoralsBIOLOGICAL REVIEWS, Issue 1 2009Fanny Houlbrčque Abstract The dual character of corals, that they are both auto- and heterotrophs, was recognized early in the twentieth Century. It is generally accepted that the symbiotic association between corals and their endosymbiotic algae (called zooxanthellae) is fundamental to the development of coral reefs in oligotrophic tropical oceans because zooxanthellae transfer the major part of their photosynthates to the coral host (autotrophic nutrition). However, numerous studies have confirmed that many species of corals are also active heterotrophs, ingesting organisms ranging from bacteria to mesozooplankton. Heterotrophy accounts for between 0 and 66% of the fixed carbon incorporated into coral skeletons and can meet from 15 to 35% of daily metabolic requirements in healthy corals and up to 100% in bleached corals. Apart from this carbon input, feeding is likely to be important to most scleractinian corals, since nitrogen, phosphorus, and other nutrients that cannot be supplied from photosynthesis by the coral's symbiotic algae must come from zooplankton capture, particulate matter or dissolved compounds. A recent study showed that during bleaching events some coral species, by increasing their feeding rates, are able to maintain and restore energy reserves. This review assesses the importance and effects of heterotrophy in tropical scleractinian corals. We first provide background information on the different food sources (from dissolved organic matter to meso- and macrozooplankton). We then consider the nutritional inputs of feeding. Finally, we review feeding effects on the different physiological parameters of corals (tissue composition, photosynthesis and skeletal growth). [source] | |||||||||||||