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 vivo and in vitro models. Methods: HDAC4 was deleted in Col2α1-Cre; HDAC4 fl/fl mice. Growth of the Col2α1-Cre; HDAC4 d/d mice was compared with HDAC4 fl/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; HDAC4 d/d mice were markedly smaller compared with the control mice. At postnatal days 14 and 21, the Col2α1-Cre; HDAC4 d/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.

Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis

“…Our data regarding both chondrocytes and the synovial membrane are in line with those reporting an increased expression of CD31 and CD34 in the knee joints of the Col2α1-Cre; mice by postnatal days 14 and 21 [ 55 ]. As both CD31 and CD34 are markers of a number of progenitor cells, their expression in the OA might be an indication of an attempt of the cells to proliferate and differentiate as well as a kind of endochondral bone formation [ 55 ].…”

[Retracted] The Status Quo of College Students’ Participation in English Online Learning in the Blended Learning Environment and the Ways to Improve It

“…Gao et al proposed that the stronger the compatibility of online education platform, the more reasonable the layout design of online education platform, the clearer the video images, and the better the audio quality, the more the college students who are willing to continue to use English online education platform for learning [11]. Kong proposed that the online education platform promoted by institution of higher learning will make full use of high-tech elements such as cloud technology and big data artificial intelligence to innovate online education mode and reshape learners' behavior.…”

Multifunctional Injectable Hydrogel Microparticles Loaded with miR‐29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by Regulating Osteogenesis and Angiogenesis

“…Previous studies have shown that decreased expression of HDAC4 activates the RUNX2 promoter, leading to upregulation of VEGF expression, thus promoting vascular formation on the growth plate. [ 48 ] To investigate the relationship between miR‐29a/HDAC4/RUNX2 and VEGF expression, we examined the gene and protein expression of VEGF in different groups in vitro. Immunofluorescence staining (Figure 8C) showed a significant decrease in HDAC4 expression and a significant increase in RUNX2 and VEGF expression in the HMP@Agomir‐29a‐Exo group.…”