| 431. |
- Nilsson, Anders, 1958, et al.
(författare)
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Hormonal regulation of longitudinal bone growth.
- 1994
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Ingår i: European journal of clinical nutrition. - 0954-3007. ; 48 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of postnatal somatic growth is complex. Genetic, nutritional factors and hormones exert regulatory functions. Hormones that have an established role in the regulation include growth hormone (GH), thyroid hormone and sex steroids. GH promotes mainly the growth of the long bones in terms of final height, while the action of the sex steroids and thyroid hormone is less well known. Longitudinal bone growth is the result of chondrocyte proliferation and subsequent endochondral ossification in the epiphyseal growth-plates. The growth-plate is a cartilaginous template that is located between the epiphysis and the metaphysis of the long bones. GH and insulin-like growth factor-I (IGF-I) have different target cells in the epiphyseal growth-plate. GH stimulates the slowly dividing prechondrocytes in the germinative cell layer while IGF-I promotes the clonal expansion in the proliferative cell layer of a GH primed cell. Thyroid hormone blocks the clonal expansion and stimulates chondrocyte maturation. IGF-I mRNA is primarily regulated by GH, and IGF-I is produced in several tissues such as the liver, muscle, fat and epiphyseal growth plates. However, IGF-I mRNA is also increased during compensatory growth of heart and kidneys and by estrogen in the Fallopian tube in the rat. Nutrition, i.e. energy from fat and carbohydrates and proteins, also influences the final height, but the cellular mechanism of action is not known. The aim of this article is to review hormonal action on longitudinal bone growth.
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| 432. |
- Nilsson, Anders K., 1982, et al.
(författare)
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Preterm infant circulating sex steroid levels are not altered by transfusion with adult male plasma: a retrospective multicentre cohort study
- 2022
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ. - 1359-2998 .- 1468-2052. ; 107:6, s. 577-582
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones delivered via plasma transfusions from adult male donors to very preterm infants do not alter the circulating plasma concentrations in the infant, irrespective of gender. Objective To determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids. Design and patients Retrospective multicentre cohort study in 19 infants born at gestational age Setting Three neonatal intensive care units in Sweden. Main outcome measures Concentrations of sex steroids and sex hormone-binding globulin (SHBG) in donor plasma and infant plasma measured before and after a plasma transfusion and at 6, 12, 24 and 72 hours. Results The concentrations of progesterone, dehydroepiandrosterone and androstenedione were significantly lower in donor plasma than in infant plasma before the transfusion (median (Q1-Q3) 37.0 (37.0-37.0), 1918 (1325-2408) and 424 (303-534) vs 901 (599-1774), 4119 (2801-14 645) and 842 (443-1684) pg/mL), while oestrone and oestradiol were higher in donor plasma (17.4 (10.4-20.1) and 16.0 (11.7-17.2) vs 3.1 (1.1-10.2) and 0.25 (0.25-0.25) pg/mL). Median testosterone and dihydrotestosterone (DHT) levels were 116-fold and 21-fold higher in donor plasma than pre-transfusion levels in female infants, whereas the corresponding difference was not present in male infants. Plasma sex steroid levels were unchanged after completed transfusion compared with pre-transfusion levels, irrespective of the gender of the receiving infant. The SHBG concentration was significantly higher in donor than in recipient plasma (22.8 (17.1-33.5) vs 10.2 (9.1-12.3) nmol/L) before transfusion but did not change in the infants after the transfusion. Conclusions A single transfusion of adult male plasma to preterm infants had no impact on circulating sex steroid levels.
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| 433. |
- Nilsson, Cecilia, et al.
(författare)
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Reductions in adipose tissue and skeletal growth in rat adult offspring after prenatal leptin exposure.
- 2003
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 176:1, s. 13-21
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is involved in regulating food intake, energy balance and bone formation. Increasing evidence suggests that leptin is also involved in fetal growth and development. The aim of this study was to determine if increased maternal leptin is followed by changes in body composition, skeletal growth or hormonal regulation in the adult rat offspring. Pregnant rats were given injections of either human recombinant leptin (3.5 mg/kg, i.p.) or vehicle on days 8, 10 and 12 of gestation. Both genders of leptin-exposed offspring showed significantly reduced adipose tIssue weight at adult age. Skeletal growth and cortical bone dimensions were significantly reduced. Circulating testosterone levels were significantly increased in female leptin-exposed offspring, and male leptin-exposed offspring had significant testicular enlargement. No significant effects were seen on circulating leptin levels or hypothalamic protein levels of the leptin receptor. The results demonstrate that maternally administered leptin is involved in fetal growth and development, leading to lean offspring with reduced skeletal growth.
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| 434. |
- Nilsson, Karin H., et al.
(författare)
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Estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other
- 2022
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 322:3, s. E211-E218
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is an age-dependent serious skeletal disease that leads to great suffering for the patient and high social costs, especially as the global population reaches higher age. Decreasing estrogen levels after menopause result in a substantial bone loss and increased fracture risk, whereas estrogen treatment improves bone mass in women. RSPO3, a secreted protein that modulates WNT signaling, increases trabecular bone mass and strength in the vertebrae of mice, and is associated with trabecular density and risk of distal forearm fractures in humans. The aim of the present study was to determine if RSPO3 is involved in the bone-sparing effect of estrogens. We first observed that estradiol (E2) treatment increases RSPO3 expression in bone of ovariectomized (OVX) mice, supporting a possible role of RSPO3 in the bone-sparing effect of estrogens. As RSPO3 is mainly expressed by osteoblasts in the bone, we used a mouse model devoid of osteoblast-derived RSPO3 (Runx2-creRspo3flox/flox mice) to determine if RSPO3 is required for the bone-sparing effect of E2 in OVX mice. We confirmed that osteoblast-specific RSPO3 inactivation results in a substantial reduction in trabecular bone mass and strength in the vertebrae. However, E2 increased vertebral trabecular bone mass and strength similarly in mice devoid of osteoblast-derived RSPO3 and control mice. Unexpectedly, osteoblast-derived RSPO3 was needed for the full estrogenic response on cortical bone thickness. In conclusion, although osteoblast-derived RSPO3 is a crucial regulator of vertebral trabecular bone, it is required for a full estrogenic effect on cortical, but not trabecular, bone in OVX mice. Thus, estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other.NEW & NOTEWORTHY Osteoblast-derived RSPO3 is known to be a crucial regulator of vertebral trabecular bone. Our new findings show that RSPO3 and estrogen regulate trabecular bone independent of each other, but that RSPO3 is necessary for a complete estrogenic effect on cortical bone.
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| 435. |
- Nilsson, Karin H., et al.
(författare)
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Osteocyte- and late osteoblast-derived NOTUM reduces cortical bone mass in mice
- 2021
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 320:5, s. E967-E975
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common skeletal disease, with increased risk of fractures. Currently available osteoporosis treatments reduce the risk of vertebral fractures, mainly dependent on trabecular bone, whereas the effect on nonvertebral fractures, mainly dependent on cortical bone, is less pronounced. WNT signaling is a crucial regulator of bone homeostasis, and the activity of WNTs is inhibited by NOTUM, a secreted WNT lipase. We previously demonstrated that conditional inactivation of NOTUM in all osteoblast lineage cells increases the cortical but not the trabecular bone mass. The aim of the present study was to determine if NOTUM increasing cortical bone is derived from osteoblast precursors/early osteoblasts or from osteocytes/late osteoblasts. First, we demonstrated Notum mRNA expression in Dmp1-expressing osteocytes and late osteoblasts in cortical bone using in situ hybridization. We then developed a mouse model with inactivation of NOTUM in Dmp1-expressing osteocytes and late osteoblasts (Dmp1-creNotum(flox/flox) mice). We observed that the Dmp1-creNotum(flox/flox) mice displayed a substantial reduction of Notum mRNA in cortical bone, resulting in increased cortical bone mass and decreased cortical porosity in femur but no change in trabecular bone volume fraction in femur or in the lumbar vertebrae L5 in Dmp1-creNotum(flox/flox) mice as compared with control mice. In conclusion, osteocytes and late osteoblasts are the principal source of NOTUM in cortical bone, and NOTUM derived from osteocytes/late osteoblasts reduces cortical bone mass. These findings demonstrate that inhibition of osteocyte/ late osteoblast-derived NOTUM might be an interesting pharmacological target to increase cortical bone mass and reduce non vertebral fracture risk. NEW & NOTEWORTHY NOTUM produced by osteoblasts is known to regulate cortical bone mass. Our new findings show that NOTUM specifically derived by DMP1-expressing osteocytes and late osteoblasts regulates cortical bone mass and not trabecular bone mass.
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| 436. |
- Nilsson, Karin H., et al.
(författare)
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RSPO3 is important for trabecular bone and fracture risk in mice and humans
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here, the authors show that RSPO3 exerts an important role for vertebral trabecular bone mass and bone strength in mice and fracture risk in humans. With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
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| 437. |
- Nilsson, L O, et al.
(författare)
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Demonstration of estrogen receptor-beta immunoreactivity in human growth plate cartilage.
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 84:1, s. 370-3
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens affect longitudinal bone growth through their action on endochondral bone formation. Two estrogen receptors are known, the classical estrogen receptor-alpha (ER alpha), newly demonstrated in human growth plate cartilage, and a recently cloned estrogen receptor-beta (ER beta). The present study aimed to localize a possible expression of ER beta protein in human growth plates. Tissue samples were obtained from tibial and femoral growth plates in four female pubertal patients undergoing epiphyseal surgery. Immunohistochemistry, using two different ER beta-specific antibodies, demonstrated positive staining for ER beta in hypertrophic epiphyseal chondrocytes from all patients. No staining was noted in resting or proliferative chondrocytes. These data suggest that in addition to ER alpha, human epiphyseal chondrocytes also express ER beta. The physiological role of ER beta in the regulation of longitudinal bone growth in humans remains to be elucidated.
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| 438. |
- Nilsson, Martin, 1966, et al.
(författare)
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Association of physical activity with trabecular microstructure and cortical bone at distal tibia and radius in young adult men
- 2010
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Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:6, s. 2917-26
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The relationship between physical activity, trabecular microstructure, and cortical geometry in weight-bearing and non-weight-bearing bone has not previously been studied in men. OBJECTIVE: The aim of this study was to investigate whether present (type and amount) and previous duration of physical activity were associated with trabecular microstructure and cortical cross-sectional area (CSA) in weight-bearing bone in young men. DESIGN AND SETTING: This was a cross-sectional, population-based study. PARTICIPANTS: Participants included a cohort of 829 Swedish men between 22.8 and 25.7 yr old (24.1 +/- 0.6 yr, mean +/- SD). MAIN OUTCOME MEASURES: Several microstructural trabecular and cortical traits were assessed with high-resolution three-dimensional peripheral quantitative computed tomography at distal tibia and radius. A standardized questionnaire was used to collect information about physical activity amount (hours per year), duration (years), and type (strain score 0-3, based on ground reaction forces). RESULTS: Men with the highest physical activity strain score had higher tibial trabecular bone volume fraction (13.9Delta%) and trabecular number (12.7%) than men with the lowest strain score (P < 0.001). Men in the group with the longest duration of physical activity had higher tibial cortical CSA (16.1%) than the sedentary men (P < 0.001). Inclusion of all physical activity variables in a linear regression model revealed that strain score independently predicted trabecular bone volume fraction, and trabecular number (P < 0.001) and that duration of previous physical activity independently predicted cortical CSA (P < 0.001) of the tibia. CONCLUSIONS: In this large cohort of young men, the degree of mechanical loading due to type of physical activity was predominantly associated with trabecular microstructure, whereas duration of previous physical activity was mainly related to parameters reflecting cortical bone size in weight-bearing bone.
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| 439. |
- Nilsson, Martin, 1966, et al.
(författare)
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Competitive physical activity early in life is associated with bone mineral density in elderly Swedish men
- 2008
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:11, s. 1557-1566
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Tidskriftsartikel (refereegranskat)abstract
- In this population-based study of 75-year-old men (n = 498), we investigated the association between physical activity (PA) early in life and present bone mineral density (BMD). We demonstrate that a high frequency of competitive sports early in life is associated with BMD at several bone sites, indicating that increases in BMD following PA are preserved longer than previously believed. Introduction Physical activity (PA) increases bone mineral density (BMD) during growth. It is unclear if the positive effects remain at old age. In this study, we aimed to determine if PA early in life was associated with BMD in elderly men. Methods In this population-based study, 498 men, 75.2 +/- .3 (mean +/- SD) years old, were included. BMD was assessed using DXA. Data concerning lifetime PA, including both competitive (CS) and recreational sports (RS), and occupational physical load (OPL), were collected at interview. Results Subjects in the highest frequency group of CS in the early period (10-35 years), had higher BMD at the total body (4.2%, p < 0.01), total hip (7.0%, p < 0.01), trochanter (8.7%, p < 0.01), and lumbar spine (7.9%, p < 0.01), than subjects not involved in CS. A stepwise linear regression model showed that frequency of CS in the early period independently positively predicted present BMD at the total body (beta=0.12, p < 0.01), total hip (beta=0.11, p < 0.01), trochanter (beta=0.12, p < 0.01), and lumbar spine (beta=0.11, p=0.01). Conclusions We demonstrate that PA in CS early in life is associated with BMD in 75-year-old Swedish men, indicating that increases in BMD following PA are preserved longer than previously believed.
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| 440. |
- Nilsson, Maria E., et al.
(författare)
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Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry.
- 2015
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:7, s. 2492-502
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Tidskriftsartikel (refereegranskat)abstract
- Accurate measurement of sex steroid concentrations in rodent serum is essential to evaluate mouse and rat models for sex steroid-related disorders. The aim of the present study was to develop a sensitive and specific gas chromatography-tandem mass spectrometry (GC-MS/MS) method to assess a comprehensive sex steroid profile in rodent serum. A major effort was invested in reaching an exceptionally high sensitivity for measuring serum estradiol concentrations. We established a GC-MS/MS assay with a lower limit of detection for estradiol, estrone, testosterone, dihydrotestosterone, progesterone, androstenedione and dehydroepiandrosterone of 0.3, 0.5, 4, 1.6, 8, 4 and 50 pg/ml, respectively, while the corresponding values for the lower limit of quantification were 0.5, 0.5, 8, 2.5, 74, 12 and 400 pg/ml, respectively. Calibration curves were linear, intra- and inter-assay CVs were low and accuracy was excellent for all analytes. The established assay was used to accurately measure a comprehensive sex steroid profile in female rats and mice according to estrus cycle phase. In addition, we characterized the impact of age, sex, gonadectomy, and estradiol treatment on serum concentrations of these sex hormones in mice. In conclusion, we have established a highly sensitive and specific GC-MS/MS method to assess a comprehensive sex steroid profile in rodent serum in a single run. This GC-MS/MS assay has, to the best of our knowledge, the best detectability reported for estradiol. Our method therefore represents an ideal tool to characterize sex steroid metabolism in a variety of sex steroid-related rodent models and in human samples with low estradiol levels.
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