Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Post-weaning epiphysiolysis causes distal femur dysplasia and foreshortened hindlimbs in fetuin-A-deficient mice

ABSTRACT: Fetuin-A / α2-Heremans-Schmid-glycoprotein (gene name Ahsg) is a systemic inhibitor of ectopic calcification. Due to its high affinity for calcium phosphate, fetuin-A is highly abundant in mineralized bone matrix. Foreshortened femora in fetuin-A-deficient Ahsg-/- mice indicated a role for fetuin-A in bone formation. We studied early postnatal bone development in fetuin-A-deficient mice and discovered that femora from Ahsg-/- mice exhibited severely displaced distal epiphyses and deformed growth plates, similar to the human disease slipped capital femoral epiphysis (SCFE). The growth plate slippage occurred in 70 % of Ahsg-/- mice of both sexes around three weeks postnatal. At this time point, mice weaned and rapidly gained weight and mobility. Epiphysis slippage never occurred in wildtype and heterozygous Ahsg+/- mice. Homozygous fetuin-A-deficient Ahsg-/- mice and, to a lesser degree, heterozygous Ahsg+/- mice showed lesions separating the proliferative zone from the hypertrophic zone of the growth plate. The hypertrophic growth plate cartilage in long bones from Ahsg-/- mice was significantly elongated and V-shaped until three weeks of age and thus prior to the slippage. Genome-wide transcriptome analysis of laser-dissected distal femoral growth plates from 13-day-old Ahsg-/- mice revealed a Jak-Stat-mediated inflammatory response including a 550-fold induction of the chemokine Cxcl9. At this stage, vascularization of the elongated growth plates was impaired, which was visualized by immunofluorescence staining. Thus, fetuin-A-deficient mice may serve as a rodent model of growth plate pathologies including SCFE and inflammatory cartilage degradation.

ORGANISM(S): Mus musculus

PROVIDER: GSE105139 | GEO | 2017/10/19

SECONDARY ACCESSION(S): PRJNA414918

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Analysis of human fetuin peptides originating from the serum of individuals, part 2

Project description:Human fetuin, also known as α-2-HS glycoprotein, is an abundant glycoprotein circulating in human plasma. AHSG is the gene symbol responsible for coding the fetuin protein. A frequent polymorphism of AHSG results in two alleles, AHSG*1 and AHSG*2, which producing three genotypes (AHSG*1, AHSG*2, and heterozygous AHSG1/2). The backbone amino acid sequences of fetuin coded by AHSG*1 and AHSG*2 genes differ from each other in two amino acids including one O-glycosylation site (position 256). We aim to describe human’s individual fetuin proteoform profiles directly isolated from serum of healthy and septic people, focusing on potential glycoproteogenomics correlations, e.g. how gene polymorphisms may affect glycosylation.

2019-05-20 | PXD012465 | Pride

Transcription profiling of rat proximal femoral growthplate after mid-shaft fracture

Project description:Mid-shaft fracture stimulates bone lengthening by increasing linear growth at the growthplate. This project studied changes in mRNA in the proximal growthplate after a mid-shaft fracture in a rat model. Experiment Overall Design: Study of rat proximal femoral growthplate after mid-shaft fracture in 4 week old Sprague-Dawley female rats. RNA from two rats were pooled for each sample. Proximal femoral growthplate was studied from the fractured femora and the intact contralateral femora.

2008-06-12 | E-GEOD-3298 | biostudies-arrayexpress

Epigentic profiling of murine proximal and distal femoral growth plates at E15.5 of mouse gestation

Project description:GWAS have identified hundreds of loci associated with height.However, determining causal mechanisms is challenging, especially since height-relevant tissues such as the growth plate are difficult to study. To discover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology and are enriched at height GWAS loci, particularly near differentially expressed growth plate genes. These regions are also enriched in binding motifs of transcription factors with known roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at the CHYS1 locus, we identified a potentially causal variant overlapping an open chromatin region and predicted to alter binding of HOXD13, important for skeletal development. Thus, integrating biologically relevant epigenetic information (here, from mouse growth plate) with genetic association results can identify biological mechanisms important for human growth.

2017-12-05 | GSE100585 | GEO

HGPC, in monolayer, 0.5 vs. 20% serum

Project description:Human growth plate chondrocytes were isolated from the distal femoral growth plate from a single adolescent undergoing epiphysiodesis. Cell were isolated and grown in monolayers, long term. Cells were replated and cultured in 0.5% or 20% serum. Keywords: parallel sample

2004-04-13 | GSE1277 | GEO

HGPC, in monolayer, 0.5% serum

Project description:Human growth plate chondrocytes were isolated from the distal femoral growth plate from 3 different adolescents undergoing epiphysiodesis. Cell were isolated and grown in monolayers, long term, in 20% serum. Cells were replated and cultured 48 h in 0.5% serum. Keywords: repeat sample

2004-04-13 | GSE1278 | GEO

Altered cartilage gene expression in Aga2 OI mouse negatively impacts linear growth through Sox9 and FGF signaling

Project description:Osteogenesis Imperfecta is characterized by short stature however the cellular mechanisms behind this phenotype are unclear. We isolated tibial and femoral cartilage growth plate chondrocytes from postnatal day 5 wild type and Aga2 (a model of OI) mice and analyzed differential expression patterns using single cell RNA-seq

2023-09-01 | GSE231795 | GEO

Gene Expression Across the Human Growth Plate

Project description:Chondrocytes advance through the long bone growth plate in synchrony, allowing their segregation into one of four zones each corresponding to a different phase of maturation. Beginning from the epiphysis the recognized zones are: reserve, proliferative, prehypertrophic, and hypertrophic. A fifth zone, the perichondrium is located in apposition to the growth plate at its circumferential surface. The progression of chondrocytes through these zones, and hence growth, is regulated by a complex interplay of signaling pathways, defects in which lead to osteochondrodysplasias. At present, there are over 370 recognized skeletal disorders, slightly more than half of which have been explained at the molecular level. Through a combination of laser microdissection, linear mRNA amplification, and GeneChip analysis, our laboratory has acquired the zone specific expression profile of chondrocytes from the distal femoral growth plates of two normal patients. On average, transcripts interrogated by 12,193 or 18,454 GeneChip probe sets (out of a possible 54,000 probe sets) were present in patients 1 and 2, respectively. The homologous inter-array correlations for the log(2) intensities were M-bM-^IM-% 0.91M-BM-10.01. Keywords: Chondrocyte differentiation program. Populations of cells corresponding to the hypertrophic, prehypertrophic, proliferative, reserve, and perichondrium, were separately isolated by laser microdissection from cryostat sections of human growth plates using a Leica AS-LMD microscope. RNA was prepared from the isolated cells, amplified using a T7 linear amplification protocol, and analyzed by hybridization to Affymetrix microarrays. The distal femoral growth plate (left or right) was exclusively used for this study. Patient 1 of this study is an 11-10/12 year old Caucasian female and patient 2 is a 13-3/12 year old Caucasian male.

2013-09-13 | E-GEOD-9160 | biostudies-arrayexpress

Sorting of Growth Plate Chondrocytes Allows the Isolation and Characterization of Cells of a Defined Differentiation Status

Project description:Axial growth of long bones occurs through a coordinated process of growth plate chondrocyte proliferation and differentiation. This maturation of chondrocytes is reflected in a zonal change in gene expression and cell morphology from resting to proliferative, prehypertrophic, and hypertrophic chondrocytes of the growth plate followed by ossification. A major experimental limitation in understanding growth plate biology and pathophysiology is the lack of a robust technique to isolate cells from the different zones, particularly from small animals. Here, we report on a new strategy for separating distinct chondrocyte populations from mouse growth plates. By transcriptome profiling of microdissected zones of growth plates, we identified novel, zone-specific cell surface markers and used these for flow cytometry and immunomagnetic cell separation to quantify, enrich, and characterize chondrocytes populations with respect to their differentiation status. This approach provides a novel platform to study cartilage development and characterize mouse growth plate chondrocytes to reveal unique cellular phenotypes of the distinct subpopulations within the growth plate.

2020-02-29 | GSE144362 | GEO

Transcription profiling of human growth plate chrondrocytes grown in monolayer, 0.5 vs. 20% serum

2008-06-12 | E-GEOD-1277 | biostudies-arrayexpress

Gene Expression Across the Human Growth Plate

2013-09-13 | GSE9160 | GEO