Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA127409 | ENA |
REPOSITORIES: ENA
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Project description:Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration. The effect of Cyclopamine on expression of Hedgehog, angiogenesis and axon guidance marker genes was analyzed by seeding a coculture of 92% hMSCs and 8% huvEC supplemented or not in cyclopamine, for 12 days
2012-09-01 | E-GEOD-22293 | biostudies-arrayexpress
Project description:Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration.
2012-09-01 | GSE22293 | GEO
Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, and skin fibroblasts (FB). We assessed uniquely accessible enhancers facilitating bone regeneration potential.
2023-04-03 | GSE182496 | GEO
Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, chondrocytes (CH) and skin fibroblasts (FB). We assessed active regulatory regions facilitating bone-regeneration potential.
2023-04-03 | GSE182495 | GEO
Project description:Appendicular skeletal growth and bone mass acquisition are controlled by a variety of growth factors, hormones, and mechanical forces in a dynamic process called endochondral ossification. In long bones, chondrocytes in the growth plate proliferate and undergo hypertrophy to drive bone lengthening and mineralization. Pleckstrin homology (PH) domain and leucine rich repeat phosphatase 1 and 2 (Phlpp1 and Phlpp2) are serine/threonine protein phosphatases that regulate cell proliferation, survival, and maturation via Akt, PKC, Raf1, S6k, and other intracellular signaling cascades. Germline deletion of Phlpp1 suppresses bone lengthening in part through parathyroid hormone receptor-dependent signaling in growth plate chondrocytes. Here, we demonstrate that Phlpp2 does not regulate endochondral ossification, and we define the molecular differences between Phlpp1 and Phlpp2 in chondrocytes. Phlpp2-/- mice are phenotypically indistinguishable from their wildtype (WT) littermates, with similar bone length, bone mass, and growth plate dynamics. Deletion of Phlpp2 had moderate effects on the chondrocyte transcriptome and proteome compared to WT cells. By contrast, Phlpp1/2-/- (double knockout) mice resembled Phlpp1-/- mice phenotypically and chondrocyte phospho-proteomes of Phlpp1-/- and Phlpp1/2-/- chondrocytes were different than WT and Phlpp2-/- chondrocyte phospho-proteomes. Data integration via multiparametric analysis identified alterations in Pdpk1 and Pak1/2 signaling pathways in chondrocytes lacking Phlpp1. In conclusion, these data demonstrate that Phlpp1, but not Phlpp2, regulates endochondral ossification through multiple and complex signaling cascades.
2024-10-22 | PXD055563 | Pride
Project description:In this study, we have analyzed DNA methylation characteristics of human mesenchymal stem and progenitor cells (MSPCs) form different tissue sources including bone marrow (BM), white adipose tissue (WAT ), umbilical cord (UC) as well as dermal fibroblasts by using the HumanMethylation450K array. Cells able to form bone through endochondral ossification and attract bone marrow in an innovative in vivo model were compared to cells lacking these capacities. Interestingly only BM-derived MSPCs were capable of bone formation and marrow attraction. These features correlated with unique epigenetic characteristics potentially enabling BM-derived cells to undergo endochondral ossification. 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2015-02-04 | E-GEOD-41933 | biostudies-arrayexpress
Project description:Bone fracture healing requires skeletal stem cells (SSCs), which facilitate intramembranous ossification and endochondral ossification in long bone fractures. Although the periosteum is necessary for bone homeostasis and regeneration, the in vivo origin and regulatory mechanisms of periosteal SSCs (P-SSCs) remain unclear. Here, we identified Postn+ P-SSCs at the cambium layer of the periosteum that actively orchestrate regeneration in response to bone injury. Notably, the Postn+ P-SSCs that arise during bicortical fractures are likely derived from Gli1+ P-SSCs. In addition, Postn+ cell ablation compromises cortical bone homeostasis and bone regeneration. The IGF signal is indispensable in the regulatory effect of Postn+ P-SSCs on bicortical fractures since the genetic deletion of Igf1r in Postn+ cells dampens bone fracture healing. Taken together, adult Postn+ cells are region-specific P-SSCs that contribute to bone homeostasis and regeneration and are partially dependent upon IGF signaling.
2024-10-16 | GSE255137 | GEO
Project description:In this study, we have analyzed DNA methylation characteristics of human mesenchymal stem and progenitor cells (MSPCs) form different tissue sources including bone marrow (BM), white adipose tissue (WAT ), umbilical cord (UC) as well as dermal fibroblasts by using the HumanMethylation450K array. Cells able to form bone through endochondral ossification and attract bone marrow in an innovative in vivo model were compared to cells lacking these capacities. Interestingly only BM-derived MSPCs were capable of bone formation and marrow attraction. These features correlated with unique epigenetic characteristics potentially enabling BM-derived cells to undergo endochondral ossification.
2015-02-04 | GSE41933 | GEO
Project description:During endochondral fracture repair, a myriad of biochemical and phenotypic changes occur at the chondro-osseuous junction that regulate cartilage to bone conversion. Osteogenic and angiogenic factors have long been studied for accelerating fracture repair. In our concise study, we focused on the neurotrophic factor nerve growth factor (NGF) and its receptor tropomyosin receptor kinase A (TRKA) as understudied therapeutic targets for accelerating endochondral fracture repair. We first characterized endogenous expression of NGF and TRKA during endochondral repair of tibial fractures. We then analyzed gene expression data from β-NGF stimulated hypertrophic cartilage and observed a promotion in endochondral ossification associated markers. Additional gene ontology analyses revealed promotion of genes associated with Wnt activation, PDGF binding, and integrin binding. Subsequent histological analyses of in vivo samples confirmed Wnt activation following local β-NGF injections via reporter mice. Finally, we tested the therapeutic efficacy of local β-NGF injections in mice, which resulted in a decrease of cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate the ability for β-NGF to promote endochondral fracture repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during endochondral ossification.
2020-12-22 | GSE150092 | GEO
Project description:Two distinct and anatomically restricted modes of ossification, which are endochondral ossification and intramembranous ossification, govern osteogenesis and joint formation throughout the human skeleton and, to our knowledge, the cellular bases by which they form and mature remain incompletely described in human development at single-cell resolution. To address this, we apply single-nuclei paired RNA and ATAC sequencing to decipher the molecular gene regulatory programmes that mediate maturation of the distinct bone and joint-forming niches in the cranium and appendicular skeleton across space and time from 5-11 PCW.
2024-10-09 | E-MTAB-14385 | biostudies-arrayexpress