| 301. |
- Kindblom, Jenny, 1971, et al.
(författare)
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Pubertal timing predicts previous fractures and BMD in young adult men: the GOOD study.
- 2006
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 21:5, s. 790-5
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Tidskriftsartikel (refereegranskat)abstract
- The importance of pubertal timing for adult BMD in males was studied through association of pubertal timing with young adult bone phenotype. Pubertal timing was found to predict both cortical and trabecular volumetric BMD and previous fractures in young adult men. Thus, late puberty is a risk factor for low BMD and previous fractures in young adult men. INTRODUCTION: Peak bone mass (PBM), achieved during puberty, is a determinant of the risk for osteoporosis and future fractures. The role of variations within the normal range in pubertal timing for fractures during pubertal development and for adult bone mass in men is unknown. MATERIALS AND METHODS: The aim of this study was to investigate the importance of pubertal timing for adult BMD and for fractures before achievement of PBM in men. The population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a well-characterized cohort of young adult Swedish males 18-20 years of age. Detailed growth charts from birth to 18-20 years of age were retrieved for 642 men participating in the GOOD study. Age at peak height velocity (PHV) was estimated and used as an assessment of pubertal timing. The skeletal phenotype was analyzed at young adult age using DXA and pQCT and previous fractures were assessed by questionnaires. RESULTS: Age at PHV was a negative independent predictor of both adult cortical and trabecular volumetric BMD and of total body and radius areal BMD. Moreover, age at PHV was associated with previous fractures in a logistic regression analysis. The OR for cortical osteopenia was 2.49 (95% CI, 1.91-3.24; p < 0.001) and for previous upper limb fractures was 1.35 (95% CI, 1.04-1.75; p < 0.05) per year increment in age at PHV. CONCLUSIONS: Age at PHV is a negative independent predictor of BMD and a positive predictor of previous fractures in young adult men. Longitudinal studies to determine if pubertal timing also predicts BMD and fractures in elderly men are required.
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| 302. |
- Klingberg, Eva, et al.
(författare)
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Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density, fractures, and syndesmophytes
- 2013
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 15:6, s. 179-179
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.METHODS: High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.RESULTS: The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (rS = 0.762; P < 0.001), and tibia (rS = 0.712; P < 0.001). When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016). mSASSS correlated negatively with trabecular vBMD in lumbar spine (rS = -0.620; P < 0.001), radius (rS = -0.400; p = 0.001) and tibia (rS = -0.475; p < 0.001) and also with trabecular thickness in radius (rS = -0.528; P < 0.001) and tibia (rS = -0.488; P < 0.001). Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (rS = 0.636; P < 0.001).CONCLUSIONS: Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.
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| 303. |
- Klingberg, Sofia, 1979, et al.
(författare)
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Characteristics of under- and over-reporters of energy intake among 18-20-year-old males: the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study
- 2008
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Ingår i: Public Health Nutrition. - 1368-9800. ; 11:11, s. 1117-1123
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify and describe characteristics of the bias of reported energy intake of participants in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. DESIGN: A validated diet history with a detailed questionnaire and an interview was used. Body fat was analysed by dual-energy X-ray absorptiometry. The ratio of energy intake (EI) to BMR was used to define under-reporters (EI:BMR < 1.30), acceptable reporters (EI:BMR >/= 1.30 to <2.64) and over-reporters (EI:BMR >/= 2.64). SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: A total of 695 males (18-20 years). RESULTS: Sixty-eight per cent were classed as acceptable reporters, 22 % as over-reporters and 10 % as under-reporters. The under-reporters had higher BMI and body fat percentage than acceptable reporters (P < 0.001), while over-reporters had lower BMI and body fat percentage (P < 0.001). Over-reporters had more frequent use of protein supplements than acceptable reporters and higher physical activity. Over-reporters had a more regular and under-reporters a less regular meal pattern compared with acceptable reporters. CONCLUSIONS: Important knowledge of dietary reporting bias in a previously sparsely studied population has been provided. Over-reporting of energy intake was more common than under-reporting in the present population of young men and characteristics of under- and over-reporters were identified. The GOOD study was initiated with the central aim to determine environmental and genetic factors involved in the regulation of bone and fat mass, and the nutrient data of the acceptable reporters can be used for further investigation of the health effects of energy and nutrient intake.
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| 304. |
- Knuuttila, Matias, et al.
(författare)
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Antiandrogens Reduce Intratumoral Androgen Concentrations and Induce Androgen Receptor Expression in Castration-Resistant Prostate Cancer Xenografts.
- 2018
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Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 188:1, s. 216-228
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Tidskriftsartikel (refereegranskat)abstract
- The development of castration-resistant prostate cancer (CRPC) is associated with the activation of intratumoral androgen biosynthesis and an increase in androgen receptor (AR) expression. We recently demonstrated that, similarly to the clinical CRPC, orthotopically grown castration-resistant VCaP (CR-VCaP) xenografts express high levels of AR and retain intratumoral androgen concentrations similar to tumors grown in intact mice. Herein, we show that antiandrogen treatment (enzalutamide or ARN-509) significantly reduced (10-fold, P<0.01) intratumoral testosterone and dihydrotestosterone concentrations in the CR-VCaP tumors, indicating that the reduction in intratumoral androgens is a novel mechanism by which antiandrogens mediate their effects in CRPC. Antiandrogen treatment also altered the expression of multiple enzymes potentially involved in steroid metabolism. Identical to clinical CRPC, the expression levels of the full-length AR (twofold, P<0.05) and the AR splice variants 1 (threefold, P<0.05) and 7 (threefold, P<0.01) were further increased in the antiandrogen-treated tumors. Nonsignificant effects were observed in the expression of certain classic androgen-regulated genes, such as TMPRSS2 and KLK3, despite the low levels of testosterone and dihydrotestosterone. However, other genes recently identified to be highly sensitive to androgen-regulated AR action, such as NOV and ST6GalNAc1, were markedly altered, which indicated reduced androgen action. Taken together, the data indicate that, besides blocking AR, antiandrogens modify androgen signaling in CR-VCaP xenografts at multiple levels.
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| 305. |
- Knuuttila, M., et al.
(författare)
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Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer
- 2018
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Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 25:9, s. 807-819
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that transmembrane protease, serine 2/ETS-related gene (TMPRSS2-ERG)-positive patients have different androgen profiles compared to TMPRSS2-ERG- negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced testosterone concentrations and increased DHT/testosterone ratios in TMPRSS2-ERG-positive tumors. TMPRSS2-ERG-positive and - negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG-positive tumors. Thus, patients with TMPRSS2-ERG-positive prostate cancer may benefit from novel inhibitors targeting the alternative DHT biosynthesis.
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| 306. |
- Kokosar, Milana, et al.
(författare)
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A Single Bout of Electroacupuncture Remodels Epigenetic and Transcriptional Changes in Adipose Tissue in Polycystic Ovary Syndrome
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- A single bout of electroacupuncture results in muscle contractions and increased whole body glucose uptake in women with polycystic ovary syndrome (PCOS). Women with PCOS have transcriptional and epigenetic alterations in the adipose tissue and we hypothesized that electroacupuncture induces epigenetic and transcriptional changes to restore metabolic alterations. Twenty-one women with PCOS received a single bout of electroacupuncture, which increased the whole body glucose uptake. In subcutaneous adipose tissue biopsies, we identified treatment-induced expression changes of 2369 genes (Q < 0.05) and DNA methylation changes of 7055 individual genes (Q = 0.11). The largest increase in expression was observed for FOSB (2405%), and the largest decrease for LOC100128899 (54%). The most enriched pathways included Acute phase response signaling and LXR/RXR activation. The DNA methylation changes ranged from 1-16%, and 407 methylation sites correlated with gene expression. Among genes known to be differentially expressed in PCOS, electroacupuncture reversed the expression of 80 genes, including PPAR gamma and ADIPOR2. Changes in the expression of Nr4 alpha 2 and Junb are reversed by adrenergic blockers in rats demonstrating that changes in gene expression, in part, is due to activation of the sympathetic nervous system. In conclusion, low-frequency electroacupuncture with muscle contractions remodels epigenetic and transcriptional changes that elicit metabolic improvement.
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| 307. |
- Kokosar, Milana, et al.
(författare)
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Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed "gene-CpG" probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease.
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| 308. |
- Kokosar, Milana, et al.
(författare)
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Erratum: Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome.
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Scientific Reports 6: Article number: 22883; Published online: 15 March 2016; Updated: 09 May 2016 This Article contains errors. In Table 3, the text in the first row ‘Down-regulated genes’ was incorrectly given as ‘Up-regulated genes’. In addition, Fig. 2E was incorrectly labeled as Fig. 2ES. The correct Fig.
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| 309. |
- Koromani, F., et al.
(författare)
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The "GEnomics of Musculo Skeletal Traits TranslatiOnal NEtwork": Origins, Rationale, Organization, and Prospects
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Musculoskeletal research has been enriched in the past ten years with a great wealth of new discoveries arising from genome wide association studies (GWAS). In addition to the novel factors identified by GWAS, the advent of whole-genome and whole-exome sequencing efforts in family based studies has also identified new genes and pathways. However, the function and the mechanisms by which such genes influence clinical traits remain largely unknown. There is imperative need to bring multidisciplinary expertise together that will allow translating these genomic discoveries into useful clinical applications with the potential of improving patient care. Therefore "GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork" (GEMSTONE) aims to set the ground for the: 1) functional characterization of discovered genes and pathways; 2) understanding of the correspondence between molecular and clinical assessments; and 3) implementation of novel methodological approaches. This research network is funded by The European Cooperation in Science and Technology (COST). GEMSTONE includes six working groups (WG), each with specific objectives: WG1-Study populations and expertise groups: creating, maintaining and updating an inventory of experts and resources (studies and datasets) participating in the network, helping to assemble focus groups defined by phenotype, functional and methodological expertise. WG2-Phenotyping: describe ways to decompose the phenotypes of the different functional studies into meaningful components that will aid the interpretation of identified biological pathways. WG3 Monogenic conditions - human KO models: makes an inventory of genes underlying musculoskeletal monogenic conditions that aids the assignment of genes to GWAS signals and prioritizing GWAS genes as candidates responsible for monogenic presentations, through biological plausibility. WG4 Functional investigations: creating a roadmap of genes and pathways to be prioritized for functional assessment in cell and organism models of the musculoskeletal system. WG5 Bioinformatics seeks the integration of the knowledge derived from the distinct efforts, with particular emphasis on systems biology and artificial intelligence applications. Finally, WG6 Translational outreach: makes a synopsis of the knowledge derived from the distinct efforts, allowing to prioritize factors within biological pathways, use refined disease trait definitions and/or improve study design of future investigations in a potential therapeutic context (e.g. clinical trials) for musculoskeletal diseases.
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| 310. |
- Korotkova, Marina, 1954, et al.
(författare)
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Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats.
- 2004
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Ingår i: The British journal of nutrition. - 0007-1145. ; 92:4, s. 643-8
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Tidskriftsartikel (refereegranskat)abstract
- PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6+n-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0.4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6+n-3 group than in the other groups. Cortical bone thickness in the n-6+n-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning.
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