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Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo
- Source :
- Molecular Medicine, Vol 26, Iss 1, Pp 1-10 (2020), Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- Background HDAC4 is a key regulator of chondrocyte hypertrophy and skeletal development, but it is not clear whether the increase in vascular invasion at growth plates is related to HDAC4 expression. To determine it, we investigated the relationship between HDAC4 and angiogenesis in both in vivo and in vitro models. Methods HDAC4 was deleted in Col2α1-Cre; HDAC4fl/fl mice. Growth of the Col2α1-Cre; HDAC4d/d mice was compared with HDAC4fl/fl mice at postnatal days 2, 4, 6, and 8. X-rays were taken to examine skeletal development. At postnatal days 14 and 21, mice were euthanized for specimen collection. Murine chondrocytes were isolated from the ventral parts of rib cages of 6-day-old mice (C57Bl/6) and transfected with a vector expressing HDAC4 as a fusion protein with green fluorescent protein (GFP). Relative expression levels of HDAC4, VEGF, and Hif1α were measured in these cells by Western blot, RT-qPCR, enzyme-linked immunosorbent, histology, and immunohistochemistry assays. Results The Col2α1-Cre; HDAC4d/d mice were markedly smaller compared with the control mice. At postnatal days 14 and 21, the Col2α1-Cre; HDAC4d/d mice exhibited a shortened growth plate, a larger secondary ossification center, and stronger staining of CD31 and CD34 compared to control mice. The isolated chondrocyte cells exhibited a high transfection efficiency of HDAC4 which resulted in the detection of a significant decrease in VEGF and Hif1α levels compared with the control chondrocytes. Conclusions HDAC4 expression in chondrocytes contributes to angiogenesis in the growth plate, and its absence in vivo negatively affects growth plates.
- Subjects :
- CD31
Angiogenesis
Gene Expression
Neovascularization, Physiologic
Chondrocyte hypertrophy
Mice, Transgenic
Histone deacetylase 4
Chondrocyte
Histone Deacetylases
Green fluorescent protein
lcsh:Biochemistry
Mice
Chondrocytes
Western blot
In vivo
Genes, Reporter
Genetics
medicine
Animals
lcsh:QD415-436
Molecular Biology
Collagen Type II
Genetics (clinical)
Mice, Knockout
medicine.diagnostic_test
Chemistry
lcsh:RM1-950
Cell Differentiation
Molecular biology
Immunohistochemistry
medicine.anatomical_structure
Phenotype
lcsh:Therapeutics. Pharmacology
Specimen collection
Molecular Medicine
Growth plate
Chondrogenesis
Biomarkers
Gene Deletion
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 15283658 and 10761551
- Volume :
- 26
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine
- Accession number :
- edsair.doi.dedup.....fb1368b7f6c9428117768502d9955228