CIDR_Genetic Determinants of Bone Fragility
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA75697 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Poor bone quality (BQ) is a major factor in skeletal fragility in the elderly. Molecular mechanisms establishing and maintaining BQ, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in BQ results from suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with an osteocyte-intrinsic repression of TGFbeta signaling (TbetaRIIocy-/-) that suppresses PLR. Control-aged bone displayed decreased TGFbeta signaling and PLR, but aging male TbetaRIIocy-/- bone did not worsen existing PLR suppression. This epistatic relationship impacted collagen material behavior at the nano and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFbeta. We determine that the decline of BQ with age arises from lost osteocyte function and maintenance of collagen integrity in a TGFbeta-dependent fashion.
2023-03-14 | MSV000091488 | MassIVE
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:Extreme corneal fragility and thinning, with a high risk of catastrophic corneal rupture secondary to minimal trauma, is the major feature of brittle cornea syndrome (BCS). Expression profiling was performed with microarrays on fibroblasts from two individuals with BCS and two age and sex matched controls.
2011-12-08 | E-MEXP-3077 | biostudies-arrayexpress
Project description:Genome Organization Drives Chromosome Fragility
| PRJNA387539 | ENA
Project description:Regulatory T cells (Tregs) are a barrier to effective anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune homeostasis, Treg-restricted Nrp1 deletion in mice results in profound tumor resistant due to Treg functional fragility. Drivers of Treg fragility, the mechanistic basis of Nrp1 dependency, and the relevance of these processes for human cancer and immunotherapy remain unknown. NRP1 expression on human Tregs in melanoma and HNSCC was highly heterogeneous and correlated with prognosis. Using a mouse model of melanoma in which mutant Nrp1-deficient (Nrp1–/–) and wild type (WT) Tregs could be assessed in a competitive environment, we found that a high proportion of intratumoral Nrp1–/– Tregs produce interferon-γ (IFNγ), which in turn drove the fragility of surrounding WT Tregs, boosting anti-tumor immunity and facilitating tumor clearance. We also show that IFNγ-induced Treg fragility is required for an effective response to PD1 immunotherapy, suggesting that cancer therapies promoting Treg fragility may be efficacious .
2017-05-22 | GSE97939 | GEO
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:Type 1 and type 2 diabetes (T1D and T2D) share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, while beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alter the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role for beta cell fragility in genetic predisposition to diabetes.
2016-02-24 | PXD000859 | Pride
Project description:Genome Organization Drives Chromosome Fragility [ChIP-seq]
| PRJNA387544 | ENA
Project description:Genome Organization Drives Chromosome Fragility [END-seq]
| PRJNA387545 | ENA