Genome wide association study of bone size yields eleven loci that also affect height, bone density, osteoarthritis and fractures
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128641 | GEO | 2019/03/22
REPOSITORIES: GEO
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Project description:In the present study we analyzed the effect of primary osteoporosis and advanced donor age on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Control cells were obtained from bone marrow of femoral heads of middle-aged, non-osteoporotic donors after total hip arthroplasty. Cells were isolated from human bone marrow according to the previously described protocol (Noth et al., 2002, J Orthop Res, 20/5, 1060-1069) under agreement of the local Ethics Committee of the University of Würzburg. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Additional criteria for confirming primary osteoporosis in these donors were vertebrae fractures and advanced age. Bone marrow of middle-aged, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty due to osteoarthritis and/or hip dysplasia. RNA samples were taken from passage 1 or passage 2.
2012-02-22 | E-GEOD-35956 | biostudies-arrayexpress
Project description:In the present study we analyzed the effect of primary osteoporosis on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from human bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Bone marrow of age-matched, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty. Cells were isolated from human bone marrow according to the previously described protocol (Noth et al., 2002, J Orthop Res, 20/5, 1060-1069) under agreement of the local Ethics Committee of the University of Würzburg. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Additional criteria for confirming primary osteoporosis in these donors were vertebrae fractures and advanced age. Bone marrow of age-matched, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty due to osteoarthritis and/or hip dysplasia. RNA samples were taken from passage 1 or passage 2.
2012-02-22 | E-GEOD-35958 | biostudies-arrayexpress
Project description:<p>Osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength.
Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is the most important determinant of bone
strength and fracture risk. Between 60 and 80% of the variance of BMD of adult Caucasian women is due to heritable factors.
Final BMD is a function of peak bone mass attained during young adulthood and the subsequent rate of bone loss, which occurs
as a result of both post-menopausal estrogen loss and aging. The evidence for a genetic contribution to rate of loss in BMD is substantially
weaker than that for peak BMD. Therefore, we have focused our sample collection on the recruitment of premenopausal women, in whom we have
sought to identify the genes influencing peak BMD at the spine and hip, the two major skeletal sites of osteoporotic fracture.</p>
<p>The primary goal of this study is to identify genes that affect peak BMD in premenopausal women. Identification of these genes may:
1) lead to molecular tests that predict risk of osteoporosis and allow institution of early preventive measures; 2) provide insight
into basic bone cell biology and other factors that affect peak BMD; and 3) provide molecular targets for therapeutic agents to increase BMD.</p>
| phs000138 | dbGaP
Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures
2015-06-26 | E-GEOD-60230 | biostudies-arrayexpress
Project description:Global microarray was performed from Trans-Iliac Bone biopsy from the patient with clinically characterized Fibrogensis imperfecta ossium (FIO). A 40-year-old male patient with clinically characterized Fibrogensis imperfecta ossium (FIO) includes fragility fracture with osteomalacia (Losserâ??s zone). On examination, his height was 158 cm, weight 47 kg, body mass index (BMI) 16.5, and his blood pressure was 120/80 mmHg. He had no palpable goiter, neck masses or lymphadenopathy. He had no exostosis or bony deformity. He had difficulty in getting up from squatting position and needed a stick to help with walking. The hip joint movements were painful and restricted.. The rest of the examination including abdomen was other wise normal or non-contributory. His laboratory evaluation was as follows: hemoglobin 13.2gm/dl, total WBC 7200/mm3 and erythrocyte sedimentation rate12 mm for 1st hour. Mean ± SD (3 values) serum calcium (Ca) adjusted for albumin was 9.5 ± 1.3 mg/dl (reference range: 8.5 - 11mg/dl). Serum phosphate (PO4) was 3.5 ± 0.3 mg/dl (reference range 3.5-5.0 mg/dl), serum magnesium 1.6mg/dl (reference range 1.58-2.55 mg/dl), total alkaline phosphatase (AP) 39.6 ± 2.6 KA Units (reference range: 3 â?? 13 KA Units), serum creatinine (Cr) was 1.1 mg/dl. Liver function tests were normal. Twenty four hour mean urine Ca, and phosphorus was 65.3 and 563 mg/d, respectively. The renal tubular handling of phosphate was normal (TmP/GFR 4.2 mg/dl â?? normal 2.4-4.2). The serum intact parathyroid hormone (iPTH) level by immunochemilunometry was 19 pg/ml (reference range: 10-69 pg/ml).Serum 25-hydroxyvitamin D level was 59.9( reference range 9 â?? 37 ng/ml). Serum 1,25-hydroxyvitamin D level was 76.6 ng/ml (reference range â?? 3 ng/ml). Arterial blood gases and urine pH were within normal range. Thyroid function tests were normal. Serum tissue transglutaminase antibody (tTG) titre was negative. Urine for Bence Jones protein was negative and serum electrophoresis was normal. Radiographs of the skull and hands were normal. The lumbar spine showed â??rugger â??jerseyâ?? spine with osteopenia . Views of the pelvis showed bilateral coxa vera and bilateral femur neck fracture with â??fishnet appearanceâ??. The chest radiograph showed multiple Looser zones with fractures of several ribs. The lower end of tibia showed â??fishnet appearanceâ??, tendon calcification and new bone formation. Ultrasonography of the neck did not reveal any abnormality in the thyroid or parathyroid glands. Ultrasonography of the abdomen and KUB region was normal. A 99mTc sestamibi scan was normal. Bone mineral density (BMD) of the hip with a T-score of -2.2 SD. Magnetic resonance imaging of pelvis showed fracture of bilateral neck and hypointense marrow on T1W and T2W sequences . A 99mTc MDP bone scan showed increased radiotracer uptake bilaterally in the shoulders, elbows, wrists, small joints of hands, multiple sites at bilateral ribs, the entire vertebral column, and lower end of tibia but not the skull (beheaed scan). Transiliac bone biopsy showed thickened bony trabeculae with obliteration of marrow spaces and at places, focal areas of exaggerated osteoclastic activity. There was prominent osteoblastic proliferation as well as osteoid like areas were also seen. At places it showed sclerosis, eaten up edges of bone and foci of new calcification (bone formation). With the above mentioned clinical and investigation proile a diagnosis of FIO was considered most likely FIO may easily be misdiagnosed because of its superficial similarity to axial osteomalacia osteoporosis, and other metabolic bone disorders with pathological fractures. Bone pain or pathological fractures in a previously healthy adult should lead to radiological and biochemical investigation. Generalized increase in radiological bone density may indicate myelofibrosis or fluorosis but an increased level of alkaline phosphatase favours Pagetâ??s disease or osteomalacia. Bone biopsy suggests gross osteomalacia until the nostic process is rarely logical, but it would not be so delayed if bone sections were always examined under polarized light. There are many unsolved problems in this crippling condition. Apart from complete ignorance of the cause, yet it is not known, what is replacing the mature collagen of bone, why other collagen-containing tissues are apparently unaffected. Why patients commonly have circulating paraprotein and whether there is any effective treatment. Till date, there is no literature has been reported exploring the genes involved in the pathogenesis of FIO. Hence, aim of present study is identification of various genes involved in the regulation of various signaling pathways involved in pathogenesis of FIO. Total RNA was isolated from Trans-Iliac Bone biopsy (Control Individual (n=1) & Patient (n=1)) using TRIZOL method and global microarray was performed on Affymetrix Genechip HumanPrimview platform. The array was performed on duplicate.
2016-07-31 | E-GEOD-43861 | biostudies-arrayexpress
Project description:Studies in Aotearoa New Zealand found higher bone mineral density and lower rate of hip fracture in people of Polynesian ancestry compared to Europeans. We hypothesised that differences in osteoblast gene expression contribute to the differences in bone properties between the two groups, and aimed to identify mechanisms that underlie the bone phenotype.
2020-09-03 | GSE157322 | GEO
Project description:Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures.
2024-04-10 | PXD041546 | JPOST Repository
Project description:The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of human bone tissue and to relate it to chronological age. Toward this end, we used the epigenetic clock software described in Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928 Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 486,000 CpGs. The trabecular bone pieces were obtained from the central part of the femoral head of Spanish (Caucasian) patients with hip fractures (due to osteoporosis) or subjects with osteoarthritis. About 85% of the cell population in this bone tissue are osteocytes and the remainder are osteoblasts, bone marrow, etc.
2015-06-03 | E-GEOD-64490 | biostudies-arrayexpress
Project description:<p>Osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength.
Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is the most important determinant of bone
strength and fracture risk. Between 60 and 80% of the variance of BMD of adult Caucasian women is due to heritable factors.
Final BMD is a function of peak bone mass attained during young adulthood and the subsequent rate of bone loss, which occurs
as a result of both post-menopausal estrogen loss and aging. The evidence for a genetic contribution to rate of loss in BMD is substantially
weaker than that for peak BMD. Therefore, we have focused our sample collection on the recruitment of premenopausal women, in whom we have
sought to identify the genes influencing peak BMD at the spine and hip, the two major skeletal sites of osteoporotic fracture.</p>
<p>The primary goal of this study is to identify genes that affect peak BMD in premenopausal women. Identification of these genes may:
1) lead to molecular tests that predict risk of osteoporosis and allow institution of early preventive measures; 2) provide insight
into basic bone cell biology and other factors that affect peak BMD; and 3) provide molecular targets for therapeutic agents to increase BMD.</p>
| phs000138.v2.p1 | EGA
Project description:Stress fractures are microcracks in bone caused by repetitive loading and these microcracks can increase the risk of developing catastrophic fractures. Early detection of stress fractures can be difficult due to the necessity of accurate clinical detection. MicroRNAs could be used as potential diagnostic and prognostic biomarkers due to their size, abundance, tissue specificity and stability in body fluids. Global profiling of circulating plasma small RNA-sequencing between lame horses (stress fractures and non-stress fractures) and non-lame control horses and the effects and role of selected stress fracture-related miRNAs on equine bone marrow derived mesenchymal stem cells (BMMSCs) were investigated. The miRNA profiles of stress fracture cases and non-lame stress fracture cases were similar. No miRNA was identified for potential usage as a biomarker for differentiating stress fracture from lame cases. However, the miRNA profiles of lame cases and non-lame control horses were significantly different. RNA-sequencing showed three miRNAs (eca-miR-486-5p, eca-miR-26a and eca-miR-23a) were most significantly differentially expressed (p value <0.05) between lame cases and non-lame controls, which was validated by qPCR. Of these, eca-miR-486-5p demonstrated the most abundant and significant increased miRNA in the lame cases compared to non-lame control cases. Cell transfection experiments using the miR-486-5p mimic treatment in equine BMMSCs showed upregulation of the osteogenic transcription factor, Runt-related transcription factor 2 (RUNX2) and insulin-like growth factor type 1 (IGF1). A significant decrease of miR-133a in the miR-486-5p mimic treated cells was also demonstrated. Since RUNX2 is the known target of miR-133a, miR 486-5p together with miR-133a would suggest the biological importance of bone turnover and osteogenesis in equine BMMSCs, but further investigation of role of miR-486-5p and miR-133a in equine bone biology is warranted.
2024-05-23 | GSE268059 | GEO