Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | Molecular Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s10020-020-00154-6 |
| _version_ | 1818211150596145152 |
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| author | Lilan Gao Shengchun Li Xiaochun Wei Guoqing Du Dennis Wei Lei Wei |
| author_facet | Lilan Gao Shengchun Li Xiaochun Wei Guoqing Du Dennis Wei Lei Wei |
| author_sort | Lilan Gao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T05:27:56Z |
| format | Article |
| id | doaj.art-771f189327ff4ba192cd7dad5573b2a6 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-12T05:27:56Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-771f189327ff4ba192cd7dad5573b2a62022-12-22T00:36:25ZengBMCMolecular Medicine1076-15511528-36582020-05-0126111010.1186/s10020-020-00154-6Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivoLilan Gao0Shengchun Li1Xiaochun Wei2Guoqing Du3Dennis Wei4Lei Wei5Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of TechnologyThe Second Hospital of Shanxi Medical UniversityThe Second Hospital of Shanxi Medical UniversityShi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of TCMNortheastern UniversityDepartment of Orthopedics, Warren Alpert Medical School of Brown University / RIHAbstract 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.http://link.springer.com/article/10.1186/s10020-020-00154-6Histone deacetylase 4Growth plateMiceChondrocytesAngiogenesis |
| spellingShingle | Lilan Gao Shengchun Li Xiaochun Wei Guoqing Du Dennis Wei Lei Wei Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo Molecular Medicine Histone deacetylase 4 Growth plate Mice Chondrocytes Angiogenesis |
| title | Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo |
| title_full | Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo |
| title_fullStr | Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo |
| title_full_unstemmed | Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo |
| title_short | Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo |
| title_sort | conditional deletion of hdac4 from collagen type 2α1 expressing cells increases angiogenesis in vivo |
| topic | Histone deacetylase 4 Growth plate Mice Chondrocytes Angiogenesis |
| url | http://link.springer.com/article/10.1186/s10020-020-00154-6 |
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