Loss of Foxc1 and Foxc2 function in chondroprogenitor cells disrupts endochondral ossification.
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ABSTRACT:
PROVIDER: PRJNA698637 | ENA |
REPOSITORIES: ENA
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Project description:Endochondral ossification forms and grows the majority of the mammalian skeleton and is tightly controlled through gene regulatory networks. The forkhead box transcription factors Foxc1 and Foxc2 have been demonstrated to regulate aspects of osteoblast function in the formation of the skeleton but their roles in chondrocytes to control endochondral ossification are less clear. We demonstrate that Foxc1 expression is directly regulated by SOX9 activity, one of the earliest transcription factors to specify the chondrocyte lineages. Moreover we demonstrate that elevelated expression of Foxc1 promotes chondrocyte differentiation in mouse embryonic stem cells and loss of Foxc1 function inhibits chondrogenesis in vitro. Using chondrocyte-targeted deletion of Foxc1 and Foxc2 in mice, we reveal a role for these factors in chondrocyte differentiation in vivo. Loss of both Foxc1 and Foxc2 caused a general skeletal dysplasia predominantly affecting the vertebral column. The long bones of the limb were smaller and mineralization was reduced and organization of the growth plate was disrupted. In particular, the stacked columnar organization of the proliferative chondrocyte layer was reduced in size and cell proliferation in growth plate chondrocytes was reduced. Differential gene expression analysis indicated disrupted expression patterns in chondrogenesis and ossification genes throughout the entire process of endochondral ossification in Col2-cre;Foxc1Δ/Δ;Foxc2Δ/Δ embryos. Our results suggest that Foxc1 and Foxc2 are required for correct chondrocyte differentiation and function. Loss of both genes results in disorganization of the growth plate, reduced chondrocyte proliferation and delays in chondrocyte hypertrophy that prevents correct ossification of the endochondral skeleton.
2021-09-08 | GSE165951 | GEO
Project description:Foxc1 and Foxc2 are highly expressed in adult podocytes. To bypass embryonic lethality of Foxc1 and Foxc2 KO, mice ubiquitously expressing inducible-Cre (ROSA26-CreERT2) were mated with floxed-Foxc1 and floxed-Foxc2 mice. We used microarrays to detail effects of deletions of Foxc1 and Foxc2 on podocyte gene expression profiles in adult podocyte in vivo and in vitro.
2018-07-25 | GSE117571 | GEO
Project description: Not available
| S-EPMC8383119 | biostudies-literature
Project description:Mesenchymal cell-derived septoclasts resorb cartilage during endochondral ossification and fracture healing
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Project description:Intestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged intestinal epithelium. However, whether angiocrine factors secreted from vascular endothelial cells (ECs) - blood and lymphatic ECs (BECs and LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 and FOXC2 as essential regulators of angiocrine signaling in regeneration of the small intestine after ischemia-reperfusion (I/R) injury. EC- and LEC-specific deletions of Foxc1, Foxc2, or both in mice augment I/R-induced intestinal damage by causing defects in vascular regrowth, expression of the chemokine CXCL12 and the Wnt activator R-spondin 3 in BECs and LECs, respectively, and activation of Wnt signaling in ISCs. Treatment with CXCL12 and R-spondin 3 rescues the I/R-induced intestinal damage in EC- and LEC-Foxc mutant mice, respectively. This study provides evidence that FOXC1 and FOXC2 are required for intestinal regeneration by stimulating angiocrine CXCL12 and Wnt signaling.
2021-12-13 | GSE190581 | GEO
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:Foxc1 and Foxc2 are necessary to maintain glomerular podocytes
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Project description:We identified Fox1 and Foxc2 core transcription factors in kidney glomeruli. To investigate their transcriptional regulatory roles in glomeruli, we performed ChIPseq of Foxc1 and Foxc2 in adult mouse kidney glomeruli. The genome wide distribution of Foxc1/2 binding sites revealed they regulated the differentiation and mature state of adult podocyte to maintain kidney homeostatis.
2021-03-26 | GSE116302 | GEO
Project description:Molecular Profiling of Failed Endochondral Ossification in Mucopolysaccharidosis VII
| PRJNA533818 | ENA
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