Physical and chemical niche of human growth plate for polarized bone development
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Hongwei Ouyang
PROVIDER: PXD059908 | iProX | Thu Jan 16 00:00:00 GMT 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Here we show a multifunctional protein, Hnrnpk, is essential for preventing excessive apoptosis and premature differentiation of growth plate chondrocytes. These datas were the RNA-seq of E18.5 growth plate chondrocytes with or without Hnrnpk.
2022-09-28 | GSE197283 | GEO
Project description:Recently, skeletal stem cells were shown to be present in the epiphyseal growth plate (epSSCs), but their function in connection with linear bone growth remains unknown. Here, we explore the possibility that modulating the number of epSSCs can correct differences in leg length. First, we examined regulation of the number and activity of epSSCs by Hedgehog signaling (Hh). Both systemic activation of Hh pathway with Smoothened agonist (SAG) and genetic activation of Hh pathway by Patched (Ptch1) ablation in Pthrp-CreER;Ptch1 fl/fl;tdTomato mice promoted proliferation of epSSCs and clonal enlargement. Transient intra-articular administration of SAG also elevated the number of epSSCs. When SAG-containing beads were implanted into the femoral secondary ossification center (SOC) of one leg of rats, this leg was significantly longer one month later than the contralateral leg implanted with vehicle-containing beads, an effect that was even more pronounced two and 6 months after implantation. We conclude that Hh signaling activates growth plate epSSCs, which effectively leads to increased longitudinal growth of bones. This opens new therapeutic possibilities for the treatment of differences in leg length
2025-01-13 | GSE254020 | GEO
Project description:Lipids play a crucial role in signalling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesised to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralisation. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics. Multivariate analysis identified 96 and 80 lipid ions with differential abundances across joint tissues in juvenile and adult mice respectively. In both ages, marrow was enriched in phospholipid platelet activating factors (PAFs) and related metabolites, cortical bone had a low lipid content, while lysophospholipids were strikingly enriched in the growth plate, an active site of mineralisation and PHOSPHO1 activity. Spatially-resolved profiling of PHOSPHO1-knockout (KO) mice across the resting, proliferating, and hypertrophic growth plate zones revealed 272, 306, and 296 significantly upregulated, and 155, 220 and 190 significantly downregulated features, respectively, relative to wild type (WT) controls. Of note, phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine and phosphatidylethanolamine derived lipid ions were upregulated in PHOSPHO1-KO versus WT. Our imaging pipeline has established a spatially-resolved lipid signature of joint tissues and has demonstrated that PHOSPHO1 ablation significantly alters the growth plate lipidome, highlighting an essential role of the PHOSPHO1-mediated membrane phospholipid metabolism in lipid and bone homeostasis.
2023-04-19 | PXD038909 | Pride
Project description:In progressed puberty, estrogen is responsible for the deceleration of growth by stimulating growth plate maturation. The mechanism of action is largely unknown. We obtained pubertal growth plate specimens of the same girl at Tanner stage B2 and Tanner stage B3, which allowed us to address this issue in more detail. Histological analysis showed that progression of puberty coincided with characteristic morphological changes associated with growth plate maturation, such as decreases in total growth plate height (p=0.002), height of the individual zones (p<0.001) and a increase in intercolumnar space (p<0.001). Microarray analysis of the specimens identified 394 genes (72% upregulated, 28% downregulated) changing with progression of puberty. Overall changes in gene expression were small (average 1.1 fold change). The 394 genes mapped to 13 significantly changing pathways (p<0.05) in majority belonging to extracellular matrix, cell cycle and cell death, which are all related to growth plate maturation. We next scanned the upstream promoter regions of the 394 genes for the presence of evolutionary conserved binding sites for transcription factors implemented in growth plate maturation such as Estrogen Receptor, Androgen Receptor, Elk1, Stat5b, CREBP and Runx2. Runx2 and Elk1, but not estrogen receptor binding sites were enriched and were present in 87 and 43 out of the 394 genes, respectively.In conclusion, our data suggest a role for Runx2 and Elk1 in growth plate maturation and provides suggestive evidence that the effect of estrogen on growth plate maturation is not mediated by activating genomic estrogen signalling in growth plate chondrocytes.
2010-05-01 | GSE18338 | GEO
Project description:Stimulation of skeletal stem cells in the growth plate promotes linear bone growth.
| PRJNA1068129 | ENA
Project description:Hnrnpk orchestrates embryonic growth plate development via regulating glycolysis
| PRJNA809664 | ENA
Project description:The growth plate, which comprises sequentially differentiated cell layers, is a critical structure for bone elongation and regeneration. Although several key regulators in growth plate development have been identified using primarily genetic perturbation, the systematic understanding is still limited. Here we used single cell RNA-seq to interrogate gene expression profiles of 217 single cells from growth plates, and developed the bioinfromatics pipeline Sinova to de-novo reconstruct physiological growth plate development in both temporal and spatial high-resolution. Our unsupervised model not only confirmed prior knowledge but also enabled systematic discovery of novel genes, potential signal pathways and surface markers CD9/CD200 to precisely depict the development. Sinova further identified effective transcriptional factor portfolio directing growth plate maturation, which was cross-validated experimentally using an in-vitro EGFP-Col10a screening system. Our case demonstrated systematic reconstructing of molecular cascades of a developmental process from single-cell profiling, and the workflow is readily transferable to other physiological scenarios.
2016-06-14 | GSE76157 | GEO
Project description:In progressed puberty, estrogen is responsible for the deceleration of growth by stimulating growth plate maturation. The mechanism of action is largely unknown. We obtained pubertal growth plate specimens of the same girl at Tanner stage B2 and Tanner stage B3, which allowed us to address this issue in more detail. Histological analysis showed that progression of puberty coincided with characteristic morphological changes associated with growth plate maturation, such as decreases in total growth plate height (p=0.002), height of the individual zones (p<0.001) and a increase in intercolumnar space (p<0.001). Microarray analysis of the specimens identified 394 genes (72% upregulated, 28% downregulated) changing with progression of puberty. Overall changes in gene expression were small (average 1.1 fold change). The 394 genes mapped to 13 significantly changing pathways (p<0.05) in majority belonging to extracellular matrix, cell cycle and cell death, which are all related to growth plate maturation. We next scanned the upstream promoter regions of the 394 genes for the presence of evolutionary conserved binding sites for transcription factors implemented in growth plate maturation such as Estrogen Receptor, Androgen Receptor, Elk1, Stat5b, CREBP and Runx2. Runx2 and Elk1, but not estrogen receptor binding sites were enriched and were present in 87 and 43 out of the 394 genes, respectively.In conclusion, our data suggest a role for Runx2 and Elk1 in growth plate maturation and provides suggestive evidence that the effect of estrogen on growth plate maturation is not mediated by activating genomic estrogen signalling in growth plate chondrocytes. 2 replicate samples for each developmental stage for a total of 6 samples
2010-05-01 | E-GEOD-18338 | biostudies-arrayexpress
Project description:Growth plate chondrocytes were isolated from the distal metacarpus of young dairy cattle (all under 10 mo of age), the chondrocytes were released from the extracellular matrix by digestion with Collagenase P for 4 hours, and the various zones of the growth plate were separated by density centrifugation. The least-dense Hypertrophic Zone (HZ) cells were compared to the most-dense Reserve Zone (RZ) cells. 6 pairs of HZ vs RZ were compared by microarray.
2009-10-27 | GSE18738 | GEO
Project description:To identify the non-canocical role of ATF6α and ATF6β in the long bone growth plate, we have employed whole genome microarray expression profiling as a discovery platform.
2015-08-15 | GSE49646 | GEO