Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation

Chen, Chongwei; Wei, Xiaochun; Wang, Shaowei; Jiao, Qiang; Zhang, Yang; Du, Guoqing; Wang, Xiaohu; Wei, Fulan; Zhang, Jianzhong; Wei, Lei

doi:10.1016/j.bbamcr.2016.04.018

Cited by 26 publications

(16 citation statements)

References 44 publications

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“…Data indicate B55α binds to HDAC5 and promotes its PP2A-mediated dephosphorylation (233). PP2A also dephosphorylates HDAC4 (234) and HDAC7 (235). Acetylation can play a direct role in controlling PPP function, as evidenced by acetylation of the PP2A-interacting protein BubR1 to enhance binding to PP2A-B56.…”

Section: Cross Talk Between Ppps and Protein Acetylationmentioning

confidence: 99%

Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates

Brautigan

Shenolikar

2018

Annu. Rev. Biochem.

154

149

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Protein serine/threonine phosphatases (PPPs) are ancient enzymes, with distinct types conserved across eukaryotic evolution. PPPs are segregated into types primarily on the basis of the unique interactions of PPP catalytic subunits with regulatory proteins. The resulting holoenzymes dock substrates distal to the active site to enhance specificity. This review focuses on the subunit and substrate interactions for PPP that depend on short linear motifs. Insights about these motifs from structures of holoenzymes open new opportunities for computational biology approaches to elucidate PPP networks. There is an expanding knowledge base of posttranslational modifications of PPP catalytic and regulatory subunits, as well as of their substrates, including phosphorylation, acetylation, and ubiquitination. Cross talk between these posttranslational modifications creates PPP-based signaling. Knowledge of PPP complexes, signaling clusters, as well as how PPPs communicate with each other in response to cellular signals should unlock the doors to PPP networks and signaling "clouds" that orchestrate and coordinate different aspects of cell physiology.

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Section: Cross Talk Between Ppps and Protein Acetylationmentioning

confidence: 99%

Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates

Brautigan

Shenolikar

2018

Annu. Rev. Biochem.

154

149

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“…Chondrocyte cells were isolated from the ventral parts of rib cages that were resected from 6-day-old mice (C57Bl/ 6). The cells were subsequently cultured in F-12 media supplemented with 10% fetal bovine serum (FBS; Gibco BRL, USA) at 37°C in 5% CO 2 as previously described (Chen et al 2016a). For transfections, the cells were plated in 6-well plates and grown overnight.…”

Section: Cell Culture and Transfectionsmentioning

confidence: 99%

Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo

Gao

Wei

et al. 2020

Mol Med

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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.

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“…Furthermore, mechanical stimulation also alters the subcellular distribution of HDAC4 in these cells. Proper compression of chondrocytes promotes matrix-related gene expression through HDAC4 translocation to the nucleus (Chen et al, 2016a). This effect is dependent on PP2A-induced HDAC4 dephosphorylation.…”

Section: Hdac4mentioning

confidence: 99%

The Role of HDACs and HDACi in Cartilage and Osteoarthritis

Zhang

Yang

et al. 2020

Front. Cell Dev. Biol.

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Epigenetics plays an important role in the pathogenesis and treatment of osteoarthritis (OA). In recent decades, HDAC family members have been associated with OA. This paper aims to describe the different role of HDACs in the pathogenesis of OA through interaction with microRNAs and the regulation of relevant signaling pathways. We found that HDACs are involved in cartilage and chondrocyte development but also play a crucial role in OA. However, the distinct HDAC mechanism in the pathogenesis and treatment of OA require further investigation. Furthermore, HDAC inhibitors (HDACi) can protect cartilage from disease, which may represent a potential therapeutic approach against OA.

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Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation

Cited by 26 publications

References 44 publications

Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates

Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates

Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo

The Role of HDACs and HDACi in Cartilage and Osteoarthritis

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